Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD). Formed kinins inhibit reabsorption of NaCl through bradykinin (BK)-B 2 receptors, localized along the CD. Degradation pathway of BK by kinin-destroying enzymes in urine differs completely from that in plasma, so that ACE inhibitors are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like exopeptidase (CPY) and partly by a neutral endopeptidase (NEP). Inhibitors of CPY and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (K ATP) channel blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in rats. Only high salt intake causes hypertension in animals deficient in BK-B 2 receptors, tissue kallikrein, or kininogen. Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and K ATP channel blockers could become novel antihypertensive drugs by increase in urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed.
References
[1]
Baldwin, E. An Introduction to Comparative Biochemistry; Cambridge University Press: Cambridge, UK, 1949.
[2]
Evans, D.; Piermarini, P.; Choe, K. The multifunctional fish gill: Dominant site of gas exchange, osmoregulation, acid-base regulation, and excretion of nitrogen waste. Physiol. Rev.？2005, 85, 97–177, doi:10.1152/physrev.00050.2003. 15618479
[3]
Graham, J.B. Ion transport, osmoregulation, and acid-vase balance. In The Physiology of Fishes; Evans, D., Claiborne, J., Eds.; Raylor & Francis: Boca, London, New York, 2006.
[4]
Frey, E.; Kraut, H.; Werle, E. Einleitung und übersicht. In Das Kallikrein-Kinin-System und seine Inhibitoren; Ferdinand Enke Verlag: Stuttgart, Germany, 1968.
[5]
Kraut, H.; Frey, E.; Werle, E. Der Nachweis eines Kreislaufhormons in der Pankreasdrüse. Hoppe-Seylers Z Physiol.Chem.？1930, 189, 97–106.
[6]
Rocha e Silva, M.; Berald, W.; Rosenfeld, G. Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am. J. Physiol.？1949, 156, 261–273. 18127230
Majima, M.; Katori, M. Approaches to the development of novel antihypertensive drugs: Crucial role of the renal kallikrein-kinin system. Trends Pharmacol. Sci.？1995, 16, 239–246, doi:10.1016/S0165-6147(00)89033-1. 7667898
[9]
Katori, M.; Majima, M. Pivotal role of renal kallikrein-kinin system in the development of hypertension and approaches to new drugs based on this relationship. Jpn. J. Pharmacol.？1996, 70, 95–128, doi:10.1254/jjp.70.95. 8866749
[10]
Majima, M.; Katori, M.; Ogino, M.; Saito, M.; Sugimoto, K.; Adachi, K.; Sunahara, N.; Katoh, K.; Tatemachi, N.; Takei, Y. Failure of endogenous blood kinin levels elevated by captopril to induce hypotension in normotensive and hypertensive rats--An assay for kinin by a new ELISA. Biochem. Res.？1995, 17, 698–708.
[11]
Vio, C.P.; Figueroa, C.D. Subcellular localization of renal kallikrein by ultrastructural immunochemistry. Kidney Int.？1985, 28, 36–42, doi:10.1038/ki.1985.115. 3900530
[12]
Figueroa, C.D.; Caorsi, I.; Vio, C.P. Visualization of renal kallikrein in luminal and basolateral membranes. J. Histochem. Cytochem.？1984, 32, 1238–1240. 6386977
[13]
Figueroa, C.; MacIver, A.; Mackenzie, J.; Bhoola, K. Localization of immunoreactive kininogen and tissue kallikrein in the human nephron. Histochemistry？1988, 89, 437–442, doi:10.1007/BF00492599. 3170266
[14]
Scicli, A.; Carretero, O.; Hampton, A.; Cortes, P.; Oza, M. Site of kininogenase secretion in dog nephron. Am. J. Physiol.？1976, 230, 533–537. 1259033
[15]
Fujita, T.; Kumagai, Y.; Ikeda, Y.; Inamura, N.; Iwata, T.; Ogino, M.; Majima, M. Involvement of the renal kallikrein-kinin system in furosemide-induced natriuresis in rats. Jpn. J. Pharmacol.？2000, 84, 133–139, doi:10.1254/jjp.84.133. 11128035
[16]
Chao, J.; Chao, L. Biochemistry, regulation and potential function of kallistatin. Biol. Chem. Hoppe Seyler？1995, 376, 705–713. 9072045
[17]
Yang, T.; Terada, Y.; Nonoguchi, H.; Tsujino, M.; Tomita, K.; Marumo, F. Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY. Am. J. Physiol.？1994, 267, F325–F330. 8067393
[18]
Miwa, I.; Erd？s, E.; Seki, T. Presence of three peptides in urinary kinin (substance Z). Life Science？1968, 7, 1339–1343, doi:10.1016/0024-3205(68)90265-8.
[19]
Miwa, I.; Erd？s, E.; Seki, T. Separation of peptide components of urinary kinin (substance Z). Proc. Soc. Exp. Biol. Med.？1969, 131, 768–772. 5815451
[20]
Hial, V.; Keiser, H.; Pisano, J. Origin and content of methionyl-lysyl-bradykinin, lysyl-bradykinin and bradykinin in human urine. Biochem. Pharmacol.？1976, 25, 2499–2503, doi:10.1016/0006-2952(76)90456-1. 985572
[21]
Yoshinaga, K.; Abe, K.; Miwa, I.; Furuyama, T.; Suzuki, C. Evidence for the renal origin of urinary kinin. Experientia？1964, 20, 396–397, doi:10.1007/BF02147988. 5855687
[22]
Abe, K. Urinary excretion of kinin in man with special reference to its origin. Tohoku J. Exp. Med.？1965, 87, 175–184, doi:10.1620/tjem.87.175. 5864169
[23]
Nasjletti, A.; Colina-Chourio, J.; McGiff, J. Disappearance of bradykinin in the renal circulation of dogs: Effects of kininase inhibition. Circ. Res.？1975, 37, 59–65. 167999
[24]
Tomita, K.; Pisano, J. Binding of [3H]-bradykinin in isolated nephron segments of the rabbit. Am. J. Physiol.？1984, 246, F732–F737. 6326616
[25]
Kauker, M. Bradykinin action on the efflux of luminal 23Na in the rat nephron. J. Pharmacol. Exp. Ther.？1980, 214, 119–123. 7391964
[26]
Bachvarof, D.; Saint-Jacques, E.; Larrovee, J.; Levelsque, L.; Rioux, F.; Drapeau, G.; Marceau, F. Cloning and pharmacological characterization of the rabbit bradykinin B2 receptor. J. Pharmacol. Exp. Ther.？1995, 275, 1523–1530.
[27]
Figueroa, C.; Gonzalez, C.; Grigoriev, S.; Abd Alla, S.; Hassemann, M.; Jarnagin, K.; Müller-Ester, W. Probing for the bradykinin B2 receptor in rat kidney by anti-peptide and anti-ligand antibodies. J. Histochem. Cytochem.？1995, 43, 137–148. 7822771
[28]
Song, Q.; Wang, D.; Harley, R.; Chao, L.; Chao, J. Cellular localization of low-molecular-weight kininogen and bradykinin B2 receptor mRNA in human kidney. Am. J. Physiol.？1996, 270, F919–F926. 8764310
[29]
Tomita, K.; Pisano, J.; Knepper, M. Control of sodium and potassium transport in the cortical collecting duct of the rat. J. Clin. Invest.？1985, 76, 132–136, doi:10.1172/JCI111935. 4019771
[30]
Ardaillou, N.; Placier, S.; Zhao, J.; Baudouin, B.; Ardaillou, R. Characterization of B2-bradykinin receptors in rabbit principal cells of the collecting duct. Exp. Nephrol.？1998, 6, 534–541, doi:10.1159/000020568. 9807025
[31]
Kose, H.; Boese, S.; Glanville, M.; Gray, M.; Brown, C.; Simmmons, N. Bradykinin regulation of salt transport across mouse inner medullary collecting duct epithelium involve activation of a Ca(2+)-dependent CL(-) conductance. Br. J. Pharmacol.？2000, 131, 1689–1699, doi:10.1038/sj.bjp.0703749. 11139448
[32]
Mukai, H.; Fitzgibbon, W.; Bozeman, G.; Margolius, H.; Ploth, D. Bradykinin B2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct. Am. J. Physiol.？1996, 271, R352–R360. 8770134
[33]
Kuribayashi, Y.; Majima, M.; Katori, M. Major kininases in rat urine are neutral endopeptidase and carboxypeptidase Y-like exopeptidse. Biomed. Res.？1993, 14, 191–201.
[34]
Shima, M.; Seino, Y.; Torikai, S.; Imai, M. Intrarenal localization of degradation of atrial natriuretic peptide in isolated glomerular and cortical nephron segments. Life Sci.？1988, 43, 357–363, doi:10.1016/0024-3205(88)90113-0. 2969444
[35]
Schulz, W.; Hagler, H.; Buja, L.; Erd？s, E. Ultrastructural localization of angiotensin I-converting enzyme (EC 3.4.15.1) and neutral metalloendopeptidase (EC 3.4.24.11) in the proximal tubule of the human kidney. Lab. Invest.？1988, 59, 789–797. 2848979
[36]
Sakakibara, T.; Ura, N.; Shimamoto, K.; Ogata, H.; Ando, T.; Fukuyama, S.; Yamaguchi, Y.; Masuda, A.; Mori, Y.; Saito, S.; Ise, T.; Sasa, Y.; Yamauchi, K.; Iimura, O. Localization of neutral endopeptidase in the kidney determined by the stop-flow method. In Advances in Exerimental Medicine and Biolology; Abe, K., Moriya, H., Fujii, S., Eds.; Plenum Press: New York, NY, USA, 1989.
[37]
Ogata, H.; Ura, N.; Shimamoto, K.; Sakakibara, T.; Ando, T.; Nishimiya, T.; Nakagawa, M.; Fukuyama, S.; Masuda, A.; Yamaguchi, Y.; Ise, T.; Saito, S.; Shiiki, M.; Uno, K.; Iimura, O. A sensitive method for differential determination of kininase I, II, and neutral endopeptidase (NEP) in human urine. In Advances in Exerimental Medicine and Biolology; Abe K.;, Moriya, H.; Fujii, S., Eds.; Plenum Press: New York, NY, 1989.
[38]
Skidgel, R.; Davis, R.; Erd？s, E. Purification of a human urinary carboxypeptidase (kininase) distinct from carboxypeptidase A, B, or N. Anal. Biochem.？1984, 140, 520–531, doi:10.1016/0003-2697(84)90203-3. 6486437
[39]
Erd？s, E. Some old and some new ideas on kinin metabolism. J. Cardiovasc. Pharmacol.？1990, 15 (Suppl.), 520–524.
[40]
Wilks, S. Prolyl endopeptidase. Life Sci.？1983, 33, 2149–2157, doi:10.1016/0024-3205(83)90285-0. 6358755
[41]
Majima, M.; Ikeda, Y.; Kuribayashi, Y.; Mizogami, S.; Katori, M.; Aoyagi, T. Ebelactone B, an inhibitor of urinary carboxypeptidase Y-like kininase, prevents the development of deoxycorticosterone acetate-salt hypertension in rats. Eur. J. Pharmacol.？1995, 284, 1–11, doi:10.1016/0014-2999(95)00320-K.
[42]
Majima, M.; Shima, C.; Saito, M.; Kuribayashi, Y.; Katori, M.; Aoyagi, T. Poststatin, a novel inhibitor of bradykinin-degrading enzymes in rat urine. Eur. J. Pharmacol.？1993, 232, 181–190, doi:10.1016/0014-2999(93)90772-A. 8467857
[43]
Umezawa, H.; Aoyagi, T.; Uotani, K.; Hamada, M.; Takeuchi, Y.; Takahashi, S. Ebelactone, an inhibitor of esterase, produced by actinomysetes. J. Antibiot. (Tokyo)？1980, 33, 1594–1596. 7251497
[44]
Uotani, K.; Magasawa, H.; Kondo, S.; Aoyagi, T.; Umezawa, H. Structural studies on ebelactone A and B, esterase inhibitors produced by actinomycetes. J. Antibiot. (Tokyo)？1982, 35, 1495–1499. 7161188
[45]
Aoyagi, T.; Nagai, M.; Ogawa, K.; Kojima, F.; Okada, M.; Ikeda, T.; Hamada, M.; Takeuchi, T. Poststatin, a new inhibitor of prolyl endopeptidase, produced by streptomyces viridochromogenes MH534-30F3. I. Taxonomy, production, isolation, physico-chemical properties and biological activities. J. Antibiot. (Tokyo)？1991, 44, 949–955. 1938617
[46]
Nagai, M.; Ogawa, K.; Muraoka, Y.; Naganawa, H.; Aoyagi, T.; Takeuchi, T. Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534–30F3. II. Structure determination and inhibitory activities. J. Antibiot. (Tokyo)？1991, 44, 956–961. 1938618
[47]
Satoh, U.; Kadota, Y.; Oheda, Y.; Kuwahara, J.; Aikawa, S.; Matsuzawa, F.; Doi, H.; Aoyagi, T.; Sakuraba, H.; Itoh, K. Microbial serine carboxypeptidase inhibitors--Comparative analysis of actions on homologous enzymes derived from man, yeast and wheat. J. Antibiot. (Tokyo)？2004, 57, 316–325. 15303492
[48]
Majima, M.; Kuribayashi, Y.; Ikeda, Y.; Adachi, K.; Kato, H.; Katori, M.; Aoyagi, T. Diuretic and natriuretic effect of ebelactone B in anesthetized rats by inhibition of a urinary carboxypeptidase Y-like kininase. Jpn. J. Pharmacol.？1994, 65, 79–82, doi:10.1254/jjp.65.79. 8089934
[49]
Hayashi, I.; Majima, M.; Fujita, T.; Okumura, T.; Kumagai, Y.; Tomita, N.; Morishita, R.; Higaki, J.; Ogiwara, T. In vivo transfer of antisense oligonucleotide against urinary kininase blunts deoxycorticosterone acetate-salt hypertension in rats. Br. J. Pharmacol.？2000, 131, 820–826, doi:10.1038/sj.bjp.0703634. 11030733
[50]
Adetuyibi, A.; Mills, I. Relation between urinary kallikrein and renal function, hypertension, and excretion of sodium and water in man. Lancet？1972, ii, 203–207, doi:10.1016/S0140-6736(72)91636-4.
[51]
Margolius, H.; Horowitz, D.; Gellar, R.; Allexander, R.; Gill, J.; Pisano, J.; Keiser, H. Urinary kallikrein excretion in normal man. Relationships to sodium intake and sodium-retaining steroids. Circ. Res.？1974, 35, 812–819. 4430078
[52]
Seino, J.; Abe, K.; Otuska, Y.; Saito, T.; Irokawa, N. Urinary kallikrein excretion and sodium metabolism in hypertensive patients. Tohoku J. Exp. Med.？1975, 116, 359–367, doi:10.1620/tjem.116.359. 1188919
[53]
Zinner, S.H.; Margolius, H.S.; Rosner, B.; Keiser, H.R.; Rass, E.H. Familial aggregation of urinary kallikrein concentration in childhood: Relation to blood pressure, race and urinary electrolytes. Am. J. Epidemiol.？1976, 104, 124–132. 952282
[54]
Levy, S.B.; Lilly, J.J.; Frigon, R.P.; Stone, L.A. Urinary kallikrein and plasma renin activity as determinants of renal blood flow. J. Clin. Invest.？1977, 60, 129–138, doi:10.1172/JCI108749. 874078
[55]
Abe, K.; Seino, J.; Otsuka, Y.; Yoshinaga, K. Urinary kallikrein excretion and sodium metabolism in human hypertension. In Chemistry and Biology of the Kallikrein Kinin System in Health and Disease; Pisano, J., Austen, K.F., Eds.; Forgarty Internal Center Proceedings No.27: Washington, DC, USA, 1977; pp. 411–414.
[56]
Geller, R.; Margolius, H.; Pisano, J.; Keiser, H. Effects of mineral corticoids, altered sodium intake and adrenalectomy on urinary kallikrein. Circ. Res.？1972, 31, 857–861. 4641782
[57]
Bascands, J.; Cirolami, J.-P.; Pecher, C.; Monatti, J.P.; Manuel, Y.; Suc, J. Compared effects of a low and a high sodium diet on the renal and urinary concentration and activity of kallikrein in normal rats. J. Hypertens.？1987, 5, 311–315, doi:10.1097/00004872-198706000-00008. 3649386
[58]
Omata, K.; Carretero, O.A.; Itoh, S.; Scicli, A.G. Active and inactive kallikrein in rabbit connecting tubules and urine during low and normal sodium intake. Kidney Int.？1983, 24, 714–718, doi:10.1038/ki.1983.218. 6562279
[59]
Margolius, H.; Geller, K.; Pisano, J.; Sjoerdsma, A. Altered urinary kallikrein excretion in human hypertension. Lancet？1971, ii, 1063–1965, doi:10.1016/S0140-6736(71)90382-5.
[60]
Lechi, A.; Covi, G.; Lechi, C.; Mantero, F.; Scuro, I. Urinary kallikrein excretion in Bartter's Syndrome. J. Clin. Endocrinol. Metab.？1976, 43, 1175–1178, doi:10.1210/jcem-43-5-1175. 993321
[61]
Seino, M.; Abe, K.; Sakurai, Y.; Irokawa, N.; Yasujima, M.; Chiba, S.; Otsuka, Y.; Yoshinaga, K. Effect of spironolactone on urinary kallikrein excretion in patients with essential hypertension and in primary aldosteronism. Tohoku J. Exp. Med.？1977, 121, 111–119, doi:10.1620/tjem.121.111. 847738
[62]
Miyashita, A. Urinary kallikrein determination and its physiological role in human kidney. J. Urol.？1971, 62, 507–518.
[63]
Vio, C.P.; Figueroa, C.D. Evidence for a stimulatory effect of high potassium diet on renal kallikrein. Kidney Int.？1987, 31, 1327–1334, doi:10.1038/ki.1987.146. 3302506
[64]
Jin, L.; Chao, L.; Chao, J. Potassium supplement upregulates the expression of renal kallikrein and bradykinin B2 receptor in SHR. Am. J. Physiol.-Renal Physiol.？1999, 276, F476–F484.
[65]
Suzuki, T.; Katori, M.; Fujita, T.; Kumagai, Y.; Majima, M. Involvement of the renal kallikrein-kinin system in K+-induced diuresis and natriuresis in anesthetized rats. Eur. J. Pharmacol.？2000, 399, 223–227, doi:10.1016/S0014-2999(00)00382-4. 10884523
[66]
Fujita, T.; Hayashi, I.; Kumagai, Y.; Imamura, N.; Majima, M. Early increase in renal kallikrein excretion on administration of potassium or ATP-sensitive potassium channel blockers in rats. Br. J. Pharmacol.？1999, 128, 1275–1283, doi:10.1038/sj.bjp.0702899. 10578142
[67]
Himathongkam, T.; Duly, R.; William, G. Potassium aldosterone-renin interrelationships. J. Clin. Endocrinol. Metab.？1975, 41, 153–159, doi:10.1210/jcem-41-1-153. 1167307
[68]
Hayashi, I. A secretary mechanism of renal kallikrein by a high potassium ion; a possible involvement of ATP-sensitive potassium channel. Immunopharmacology？1999, 44, 49–55, doi:10.1016/S0162-3109(99)00110-1. 10604524
[69]
Yamanaka, M.; Hayashi, I.; Fujita, T.; Cha, S.; Endou, H.; Higashihara, M.; Majima, M. Potassium-induced increase in renal kallikrein secretion is attenuated in dissected renal connecting tubules of young spontaneously hypertensive rats. Int. Immunopharmacology？2002, 2, 1957–1964, doi:10.1016/S1567-5769(02)00180-7.
[70]
Wang, T.; Wang, W.; Klein-Robbenhaar, G.; Giebisch, G. Effects of glyburide on renal tubule transport and potassium-channel activity. Ren. Physiol. Biochem.？1995, 18, 169–182. 7481068
[71]
Kamata, Y.; Fujita, T.; Kato, T.; Hayashi, I.; Kurosaka, M.; Katori, M.; Fujita, T.; Majima, M. An ATP-sensitive potassium channel blocker suppresses sodium-induced hypertension through increased secretion of urinary kallikrein. Hypertens. Res.？2009, 32, 220–226, doi:10.1038/hr.2008.33. 19262486
[72]
Perricone, S.; Humphrey, S.; Skaletzky, L.; Graham, B.; Zandt, R. Synthesis and diuretic activity of alkyl- and arylguanidine analogs of N,N'-dyclohexyl-4-morpholinecarboxamidine in rats and dogs. J. Med. Chem.？1994, 28, 3693–3700, doi:10.1021/jm00048a005.
[73]
Meisheri, K.; Humphrey, S.; Khan, S.; Cipkus-Dubrey, L.; Smith, M. 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydrochloride (U-37883A): pharmacological characterization of a novel antagonist of vascular ATP-sensitive K+ channel openers. J. Pharmacol. Exp. Ther.？1993, 266, 655–665. 8355199
[74]
Guillemare, E.; Honore, E.; De Weille, J.; Fosset, M.; Lazdunski, M.; Meisheri, K. Functional receptors in Xenopus oocytes for U-37883A, a novel ATP-sensitive K+ channel blocker: Comparison with rat insulinoma cells. Mol. Pharmacol.？1994, 46, 139–145. 8058048
[75]
Wang, T.; Wang, W.; Klein-Robbenhaar, G.; Giebisch, G. Effects of a novel KATP channel blocker on renal tubule function and K channel activity. J. Pharmacol. Exp. Ther.？1995, 273, 1382–1389. 7791111
[76]
Stanton, B. Characterization of apical and basolateral membrane conductance of rat inner medullary collecting duct. Am. J. Physiol.？1989, 256, F862–F868. 2719119
[77]
Giebisch, G. Renal potassium channels: An overview. Kidney Int.？1995, 48, 1004–1009, doi:10.1038/ki.1995.382. 8569060
[78]
Imai, M.; Nakamura, R. Function of distal convoluted and connecting tubules studied by isolated nephron fragments. Kidney Int.？1982, 21, 5849–5856.
[79]
Wright, F.; Giebisch, G. Renal potassium: Contributions of individual nephron segments and populations. Am. J. Physiol.？1978, 235, F515–F527. 367178
[80]
Muto, S. Potassium transport in the mammalian collecting duct. Physiol. Rev.？2001, 81, 85–116. 11152755
[81]
Ward, P.E.; Margolius, H.S. Renal and urinary kallikrein. In Bradykinin Kallidin and Kallikrein. Handbook of Experimental Pharmacology; Erd？s, E.G., Wilde, A.F., Eds.; Springer-Verlag: Berlin, Heidelberg, New York, 1979.
Carretero, O.A.; Scicli, A.G. The renal kallikrein-kinin system. Am. J. Physiol.？1980, 238, F247–F255. 6990779
[84]
Mayfield, R.K.; Margolius, H.S. Renal kallikrein-kinin system. Relation to renal function and blood pressure. Am. J. Nephrol.？1983, 3, 145–155, doi:10.1159/000166704. 6307046
[85]
Margolius, H.S. Tissue kallikreins and kinins: Regulation and roles in hypertensive and diabetic diseases. Annu. Rev. Pharmacol.？1989, 29, 343–364.
[86]
Carretero, O.A.; Scicli, A.G. Kinins as regulators of blood flow and blood pressure. In Hypertension: Pathology, Diagnosis, and Management; Raven Press: New York, NY, USA, 1990.
[87]
Margolius, H.S. Kallikreins and kinins. Some unanswered questions about system characteristics and roles in human disease. Hypertension？1995, 26, 221–229. 7635529
[88]
Katori, M.; Majima, M. The renal kallikrein-kinin system: Its role as a safety valve for excess sodium intake, and its attenuation as a possible etiologic factor in salt-sensitive hypertension. Crit. Rev. Clin. Lab. Sci.？2003, 40, 43–115, doi:10.1080/713609329. 12627748
[89]
Gill, J.; Melmon, K.; Gillepsie, L.; Bartter, F. Bradykinin and renal function in normal man: Effects of adrenergic blockade. Am. J. Physiol.？1965, 209, 844–848. 5843437
[90]
B？nner, G.; Preis, S.; Schunk, U.; Toussaint, C.; Kaufmann, W. Haemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans. J. Cardiovasc. Pharmacol.？1990, 15 (Suppl. 6), 546–556.
[91]
Nakano, J. Effects of synthetic bradykinin on the cardiovascular system. Arch. Int. Pharmacodyn. Ther.？1965, 157, 1–13. 5884997
[92]
Dollery, C.; Goldberg, L.; Pentecost, B. Effects of intrarenal infusions of bradykinin and acetylcholine on renal blood flow in man. Clin. Sci.？1965, 29, 433–441. 5848699
[93]
Stein, J.; Ferris, T.; Huprich, J.; Smith, Y.; Osgood, R. Effect of renal vasodilatation on the distribution of cortical blood flow in the kidney of the dog. J. Clin. Invest.？1971, 50, 1429–1438, doi:10.1172/JCI106626. 5090058
[94]
MaGiff, J.; Itskovitz, H.; Terragno, N. The actions of bradykinin and eledoisin in the canine isolated kidney: Relation to prostaglandins. Clin. Sci. Mol. Med.？1975, 49, 125–131. 1149403
[95]
Nasjletti, A.; Colina-Choourio, J. Interaction of mineral corticoids, renal prostaglandins, and the renal kallikrein-kinin system. Fed. Proc.？1976, 35, 59–65.
[96]
Heller, J.; Kramer, H.; Horacek, V. The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting inhibition: A micropuncture study in the dog. Pflugers Archiv.？1994, 427, 219–224, doi:10.1007/BF00374527.
[97]
Roman, R.; Kadunski, M.; Sicli, A.; Carretero, O.A. Influence of kinins and angiotensin II on the regulation of papillary blood flow. Am. J. Physiol.？1988, 255, F690–F698. 2845811
[98]
Zimmerman, B.; Raich, P.; Vavrek, R.; Stewart, J. Bradykinin contribution to renal blood flow effect of angiotensin converting enzyme inhibitor in the conscious sodium-restrict dog. Circ. Res.？1990, 66, 234–240. 2153061
[99]
Kon, V.; Fogo, A.; Ichikawa, I. Bradykinin causes selective efferent arteriolar dilatation during angiotensin I converting enzyme inhibition. Kidney Int.？1993, 66, 545–550, doi:10.1038/ki.1993.279.
[100]
Mattson, D.; Roman, R. Role of kinins and angiotensin in the renal hemodynamic response to captopril. Am. J. Physiol.？1991, 260, F670–F679. 2035654
[101]
Hajj-ali, A.; Zimmerman, B. Kinin contribution to renal vasodilator effect of captopril in rabbit. Hypertension？1991, 17, 504–509. 1849501
[102]
Hajj-ali, A.; Zimmerman, B. Enhanced blood pressure and renal hemodynamic effect of chronic versus acute lisinopril administration in the rabbit. J. Pharmacol. Exp. Ther.？1992, 263, 158–162. 1328603
[103]
Komers, R.; Cooper, M. Acute renal hemodynamic effect of ACE inhibition in diabetic hyperfiltration: Role of kinins. Am. J. Physiol.？1995, 268, F588–F594. 7733315
[104]
Chen, K.; Zimmerman, B. Comparison of renal hemodynamic effect of captopril: Possible role of kinins. J. Pharmacol. Exp. Ther.？1994, 270, 491–497. 8071842
[105]
Dworkin, L.; Brenner, B. The renal circulation. In The kidney; Brenner, B.M., Ed.; WB Saunders Company: Philadelphia, London, Toronto, Montreal, Sydney, Tokyo, 1996.
[106]
Cowley, A.; Mattson, D.; Lu, H.; Roman, R. The renal medulla and hypertension. Hypertension.？1995, 25, 663–673. 7721413
[107]
Mattson, D.; Cowley, A. Kinin actions on renal papillary blood flow and sodium excretion. Hypertension.？1993, 21, 961–965. 8505107
[108]
Fenoy, F.; Scicli, A.; Carretero, O.; Roman, R. Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril. Hypertension？1991, 17, 1038–1044. 1646165
[109]
Lu, H.; Roman, R.; Mattson, D.; Cowley, A. Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats. Am. J. Physiol.？1992, 263, R1064–R1070. 1443224
[110]
Mattson, D.; Roman, R.; Cowley, A. Role of nitric oxide in renal papillary blood flow and sodium excretion. Hypertension？1992, 19, 766–769. 1592478
[111]
Webster, M.; Gilmore, J. Influence of kallidin-10 on renal function. Am. J. Physiol.？1964, 206, 714–718. 14166162
[112]
Barracough, M.; Mills, I. Effects of bradykinin on renal function. Clin. Sci.？1965, 28, 199–206.
[113]
Tomita, K.; Pisano, J.; Brug, M.; Knepper, M. Effects of vasopressin and bradykinin on anion transport by the rat cortical collecting duct Evidence for an electroneutral sodium chloride transport pathway. J. Clin. Invest.？1986, 77, 136–141, doi:10.1172/JCI112268. 3080471
[114]
Borkowski, J.; Rasom, R.; Seabrook, G.; Trumbauer, G.; Chen, H.; Hill, R.; Strader, C.; Hess, J. Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neuron. J. Biol. Chem.？1995, 270, 13706–13710, doi:10.1074/jbc.270.23.13706. 7775424
[115]
Cavla, C.; Tordiras, M.; Iliescu, R.; Saul, V.; Gross, V.; Pilz, B.; Chai, G.; Merino, V.; Pesquero, J.; Baltatu, O.; Bader, M. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension. FASEB J.？2007, 21, 1689–1698. 17289925
Alfie, M.E.; Sigmon, D.H.; Pomposiello, S.I.; Carretero, O.A. Effect of high salt intake in mutant mice lacking bradykinin-B2 receptors. Hypertension？1997, 29, 483–487. 9039146
[118]
Madeddu, P.; Varoni, M.; Palomba, D.; Emanueli, C.; Demontis, M.P.; Gilorioso, N.; Dessl-Fulgheri, P.; Sarzani, R.; Anaia, V. Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. Circulation？1997, 96, 3570–3578. 9396457
[119]
Cervenka, L.; Harrison-Bernard, L.; Dipps, S.; Primrose, G.; Imig, J.; El-Dahr, S. Early onset salt-sensitive hypertension in bradykinin B(2) receptor null mice. Hypertension？1999, 34, 176–180. 10454437
[120]
Mila, A.; Gross, V.; Plehm, R.; De Silva, J.J.; Bader, M.; Luft, F. Normal blood pressure and renal function in mice lacking the bradykinin B(2) receptor. Hypertension？2001, 37, 1473–1479. 11408397
[121]
Gainer, J.; Brown, N.; Bachvarova, M.; Bastien, L.; Maltais, I.; Marceau, F.; Bachvarov, D. Altered frequency of a promoter polymorphism of the kinin B2 receptor gene in hypertensive African-Americans. Am. J. Hypertens.？2000, 13, 1268–1273, doi:10.1016/S0895-7061(00)01215-2. 11130770
[122]
Meneton, P.; Bloch-Faure, M.; Ruetten, H.; Huang, W.; Bergaya, S.; Ceiler, D.; Martins, I.; Salmon, G.; Boulanger, C.; Nussberger, J.; Crozatier, B.; Gasc, J.; Heudes, D.; Bruneval, P.; Doetschman, T.; Menard, J.; Alhenc-Gelas, F. Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice. Proc. Nat. Acad. Sci.？2001, 98, 2634–2639, doi:10.1073/pnas.051619598.
[123]
Griol-Charhbili, V.; Sbbah, L.; Colucci, J.; Vincent, M.; Baudrie, V.; Laude, D.; Elghozi, J.; Bruneval, P.; Picard, N.; Meneton, P.; Alhenc-Gelas, F.; Richer, C. Tissue kallikrein deficiency and renovascular hypertension in the mouse. Am. J. Physiol. Integral Comp. Physiol.？2009, 296, R1385–R1391.
[124]
Picard, N.; Eladari, D.; El Moghrabi, S.; Planes, C.; Bourgeois, S.; Houillier, P.; Wang, Q.; Burnier, M.; Deschenes, G.; Knepper, M.; Meneton, P.; Chambrey, R. Defective ENaC processing and function in tissue kallikrein-deficient mice. J. Biol. Chem.？2008, 283, 4602–4611, doi:10.1074/jbc.M705664200. 18086683
[125]
Slim, R.; Torremocha, F.; Marceau, T.; Pizard, A.; Hunt, S.; Vuagnat, A.; Williams, G.; Gauthier, F.; Jeunemiitre, X.; Alhenc-Gelas, F. Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. J. Am. Assoc. Nephrol.？2002, 13, 968–976.
[126]
Madeddu, P.; Varoni, M.; Pinna-Parpaglia, P.; Glorioso, N.; Anania, V. Urinary kallikrein: A marker of blood pressure sensitivity to salt. Kidney Int.？1996, 49, 1422–1427, doi:10.1038/ki.1996.200. 8731109
[127]
Madeddu, P.; Varioni, M.; Chao, J.; Soimson, J.; Glorioso, N.; Anania, V. Kallikrein-kinin system and blood pressure sensitivity to salt. Hypertension？1997, 20, 471–477.
[128]
Madeddu, P.; Vio, C.; Straino, S.; Salis, M.; Milia, A.; Emanuelli, C. Renal phenotype of low kallikrein rats. Kidney Int.？2001, 59, 2233–2242. 11380826
[129]
Damas, J.; Adams, A. Congenital deficiency in plasma kallikrein and kininogen in the Brown Norway rat. Experientia？1980, 36, 586–587, doi:10.1007/BF01965817. 6900563
[130]
Oh-ishi, S.; Satou, K.; I, H.; Yamazaki, K.; Nakano, T. Differences in prekallikrein and high molecular kininogen levels in two strains of Brown Norway rat (Kitasato strain and Katholiek strain). Thromb. Res.？1982, 28, 143–147, doi:10.1016/0049-3848(82)90043-3. 6925403
[131]
Oh-ishi, S.; Hayashi, I.; Hayasshi, M.; Yamaki, K.; Nagano, T.; Utsunomiya, I.; Nagashima, Y. Evidence for a role of the plasma kallikrein-kinin system in acute inflammation; Reduced exudation during carrageenin- and kaolin- pleurisies in kininogen-deficient rats. Agents Actions？1986, 18, 450–454, doi:10.1007/BF01965011. 3638906
[132]
Majima, M.; Katori, M.; Hanazuka, z.; Mizogami, S.; Nakano, T.; Nakao, Y.; Mikami, R.; Uryu, H.; Okamura, R.; Mohsin, S.; Oh-ishi, S. Suppression of rat deoxycoricosterone-salt hypertension by kallikrein-kinin system. Hypertension？1991, 17, 806–813. 1710605
[133]
Yamasu, S.; Oh-ishi, S.; Hayashi, I.; Hayashi, M.; Yamaki, K.; Nakano, T.; Sunhara, N. Differentiation of kinin fractions in ureter urine and bladder urine of normal and kininogen deficient rats. J. Pharamacodyn.？1989, 12, 287–292.
[134]
Hayashi, I.; Hoshiko, S.; Manabe, O.; Oh-ishi, S. A point mutation of Alanine163 to threonine is responsible for the defective secretion of high molecular weight kininogen by the liver of Brown Norway Katholiek rats. J. Biol. Chem.？1993, 268, 17219–17224. 8349607
[135]
Rhaleb, N.-E.; Yang, X.P.; Nanba, M.; Shesely, E.G.; Carretero, O.A. Effect of chronic blockade of the kallikrein-kinin system on the development of hypertension in rats. Hypertension？2001, 37, 121–128. 11208766
[136]
Lattion, A.; Baussant, T.; Alhenc-Gelas, F.; Seidah, N.; Corvol, P.; Soubrier, F. The high-molecular-mass kininogen deficient rat expresses all kininogen mRNA species, but does not export the high-molecular-mass kininogen synthesized. FEBS Lett.？1988, 239, 59–64, doi:10.1016/0014-5793(88)80545-3. 3181425
[137]
Majima, M.; Adachi, K.; Kuribayashi, Y.; Mizogami, S.; Katori, M. Increase in vascular sensitivity to angiotensin II and epinephrine after four-day infusion of 0.3 M sodium chloride in conscious kininogen-deficient Brown Norway Katholiek rats. Jpn. J. Pharmacol.？1995, 69, 149–158, doi:10.1254/jjp.69.149. 8569052
[138]
Coleman, R.; Bagdasarian, A.; Talamo, R.; Scott, C.; Seavey, M.; Guimaraes, J.; Pierce, J.; Kaplan, A. Williams trait: Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. J. Clin. Invest.？1975, 56, 1650–1662, doi:10.1172/JCI108247. 1202089
[139]
Lacombe, M.; Varet, B.; Levey, J.-P. A hitherto undescribed plasma acting at the contact phase of blood coagulation (Flaujeac factor): Case report and coagulation studies. Blood？1975, 46, 761–768. 1174709
[140]
Wuepper, K.; Miller, R.; Lacombe, M. Flaujeac trait: Deficiency of human plasma kininogen. J. Clin. Invest.？1975, 56, 1663–1672, doi:10.1172/JCI108248. 127805
[141]
Donaldson, V.; Glueck, H.; Miller, M.; Movat, H.; Habal, F. Kininogen deficiency in Fitzgerald trait: Role of high molecular weight kininogen in clotting and fibrinolysis. J. Lab. Clin. Invest.？1976, 87, 327–337.
[142]
Hayashi, H.; Koya, H.; Kitajima, K.; Kimura, I. Coagulation factor deficiency apparently related to the Fitzgerald trait: The first case in Japan. Acta Med. Okayama？1978, 32, 81–83. 148837
[143]
Oh-ishi, S.; Ueno, A.; Ucida, Y.; Katori, M.; Hayashi, H.; Koya, H.; Kitajima, K.; Kimura, I. Abnormalities in the contact activation through factor XII in Fujiwara trait: A deficiency in both high and low molecular weight kininogen with low level of prekallikrein. Tohoku J. Exp. Med.？1981, 133, 67–80, doi:10.1620/tjem.133.67. 6785899
[144]
Oh-ishi, S.; Hayashi, I.; Utsunomiya, I.; Hayashi, M.; Yamaki, K.; Yamasu, A.; Nakano, T. Role of kallikrein-kinin system in acute inflammation: Studies on high- and low-molecular weight kininogen-deficient rats (B/N-Katholiek strain). Agents Actions？1987, 21, 384–386, doi:10.1007/BF01966523. 3687591
[145]
Majima, M.; Yoshida, O.; Mihara, H.; Muto, T.; Mizogami, S.; Kuribayashi, Y.; Katori, M.; Oh-ishi, S. High sensitivity to salt in kininogen-deficient Brown Norway Katholiek rats. Hypertension？1993, 22, 705–714. 7693588
[146]
Coleman, T.; Manning, R.J.; Norman, R.J.; Granger, H.; Guyton, A. The role of salt in experimental and human hypertension. Am. J. Med. Sci.？1972, 264, 103–110, doi:10.1097/00000441-197208000-00002. 4653113
[147]
Majima, M.; Mizogami, S.; Kuribayashi, Y.; Katori, M.; Oh-ishi, S. Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats. Hypertension？1994, 24, 111–119. 8020999
[148]
Berk, B.; Vallega, G.; Muslin, A.; Gordon, H.; Canessa, M.; Alexander, R. Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. J. Clin. Invest.？1989, 83, 822–829, doi:10.1172/JCI113964. 2537850
[149]
Sasaki, S.; Takeda, K.; Okajima, H.; Takahashi, H.; Yoshimura, M.; Nakagawa, M.; Itiji, H. Pressor responses to intracisternal injection of hypertonic NaCl in rats. J. Cardiovasc. Pharmacol.？1984, 6, 349–364, doi:10.1097/00005344-198403000-00022. 6200727
[150]
Eagan, B. Neurogenic mechanism of initiating essential hypertension. Am. J. Hypertens.？1989, 2, 357S–362S. 2688692
[151]
Elliot, A.H.; Nuzum, F.R. The urinary excretion of a depressor substance (kallikrein of Frey and Kraut) in arterial hypertension. Endocrinology？1934, 18, 462–474, doi:10.1210/endo-18-4-462.
[152]
Carretero, O.; Oza, N.; Schork, A. Renal kallikrein, plasma renin, and plasma aldosterone in renal hypertension. Acta Physiolog. Latin Am.？1974, 24, 448–452.
[153]
Horwitz, D.; Margolius, H.S.; Keiser, H.R. Effects of dietary potassium and race on urinary excretion of kallikrein and aldosterone in man. J. Clin. Endocrinol. Metab.？1978, 47, 296–299, doi:10.1210/jcem-47-2-296. 263797
[154]
Abe, K.; Yasujima, M.; Irokawa, N.; Seino, M.; Chiba, S.; Sakurai, Y.; Sato, M.; Imai, M.; SAito, K.; Ito, T.; Haryuuama, T.; Otsuka, Y.; Yoshinaga, K. The role of intrarenal vasoactive substances in the pathogenesis of essential hypertension. Clin. Sci. Mol. Med. Suppl.？1978, 4, 363s–366s.
[155]
Lechi, A.; Covi, G.; Lechi, C.; Corgati, A.; Arosio, E.; Zatti, M.; Scuro, L. Urinary kallikrein excretion and plasma renin activity in patient with essential hypertension and primary aldosteronism. Clin. Sci. Mol. Med.？1978, 55, 51–55. 668267
[156]
Keiser, H. The kallikrein-kinin system in essential hypertension. Clin. Exp. Hypertens.？1979, 2, 675–691, doi:10.3109/10641968009037136.
[157]
Mersey, J.; Williams, G.; Emanual, R.; Dlunhy, R.; Wong, P.; Moore, T. Plasma bradykinin levels and urinary kallikrein excretion in normal renin essential hypertension. J. Clin. Endocrinol. Metab.？1979, 48, 642–647, doi:10.1210/jcem-48-4-642. 429510
[158]
Shimamoto, K.; Ura, N.; Tanaka, S.; Ogasawara, A.; Nakao, T.; Nakanhashi, Y.; Chao, J.; Margolius, H.; IImura, O. Excretion of human urinary kallikrein quantity measured by a direct radioimmunoassay of human urinary kallikrein in patients with essential hypertension and secondary hypertensive diseases. Jpn. Circ. J.？1981, 45, 1092–1097.
[159]
Ura, N.; Shimamoto, K.; Nakao, T.; Ogaswara, A.; Tanaka, S.; Mita, T.; Nishimiya, T.; Iimura, O. The excretion of human urinary kallikrein quantity and activity in normal and low renin subgroups of essential hypertension. Clin. Exp. Hypertens. A.？1983, 5, 329–337, doi:10.3109/10641968309069492. 6188559
[160]
Favre, L.; Jornot, L.; Riondel, A.; Vallotton, M. Urinary excretion of renal prostaglandins, kallikrein, vasopressin and aldosterone in essential hypertension. Clin. Exp. Hypertens. A.？1985, 7, 1663–1679, doi:10.3109/10641968509073617. 3869481
[161]
Carretero, O.A.; Scicli, A.G. The kallikrein-kinin system in human and in experimental hypertension. Klin. Wochenschr.？1978, 56 (Suppl. 1), 113–125, doi:10.1007/BF01477462. 366276
[162]
Zinner, S.H.; Margolius, H.S.; Rosner, B.; Kass, E.H. Stability of blood pressure rank and urinary kallikrein concentration in childhood: An eight-year follow-up. Circulation？1978, 58, 908–915. 699259
Weinberger, M.; Miller, J.; Luft, F.; Grim, C.; Fineberg, N. Definitions and characteristics of sodium sensitivity and resistance of blood pressure. Hypertension？1986, 8 (6 Pt. 2), 127–134.
[165]
Elliott, P.; Mamot, M.; Dyer, A.; Joossens, J.; Kesteloot, H.; Stamler, R.; Stamler, J.; Rose, G. The INTERSALT study: Main results, conclusions and some implications. Clin. Exp. Hypertens. A.？1989, 11, 1025–1034, doi:10.3109/10641968909035389. 2791323
[166]
Kawasaki, T.; Delea, C.; Bartter, F.; Smith, H. The effect of high-sodium and low-sodium intake on blood pressure and other related variables in human subjects with idopathic hypertension. Am. J. Med.？1978, 64, 193–198, doi:10.1016/0002-9343(78)90045-1. 629267
[167]
Weinberger, M. Salt sensitivity; does it play an important role in the pathogenesis and treatment of hypertension? Curr. Opin. Nephrol. Hypertens.？1996, 5, 205–208, doi:10.1097/00041552-199605000-00003.
[168]
Weinberger, M.; Fineberg, N. Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Hypertension？1991, 18, 67–71. 1860713
[169]
Katori, M.; Majima, M. A missing link between a high salt intake and blood pressure increase. J. Pharmacol. Sci.？2006, 100, 370–390, doi:10.1254/jphs.CRJ06003X. 16651701
[170]
Katori, M.; Majima, M. Are all individuals equally sensitive in the blood pressure to high salt intake? Acta Physiol. Hung.？2008, 95, 247–265, doi:10.1556/APhysiol.95.2008.3.2. 18788465
[171]
B？？nner, G.; Thieven, B.; R？？tten, H.; Chrosch, R.; Krone, W. Renal kallikrein is a determinant of salt sensitivity. J. Hypertens.？1993, 11 (Suppl. 5), S210–211.
[172]
Ferri, C.; Bellini, C.; Carlomagno, A.; Perrone, A.; Santucci, A. Urinary kallikrein and salt sensitivity in essential hypertensive males. Kidney Int.？1994, 46, 780–788, doi:10.1038/ki.1994.333. 7996800
[173]
Katori, M.; Majima, M.; Mohsin, S.S.J.; Hanazuka, M.; Mizogami, S.; Oh-ishi, S. Essential role of kallikrein-kinin system in suppression of blood pressure rise during developmental stage of hypertension induced by deoxycorticosterone acetate–salt in rats. Agents Actions Suppl.？1992, 38 (Pt.3), 235–242. 1281379
[174]
Okamoto, K.; Aoki, K. Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J.？1963, 27, 282–293.
Ader, J.-L.; Pollock, D.; Butterfield, M.; Arendshorst, W. Abnormalities in kallikrein excretion in spontaneously hypertensive rats. Am. J. Physiol.？1985, 248, F396–F403. 3844907
Ader, J.-L.; Tran-Van, T.; Praddaude, F. Reduced urinary kallikrein activity in rats developing spontaneous hypertension. Am. J. Physiol.？1987, 252, F964–F969. 3647733
[179]
Mohsin, S.S.J.; Majima, M.; Katori, M.; Sharma, J.N. Important suppressive roles of the kallikrein-kinin system during the developmental stage of hypertension in spontaneously hypertensive rats. Asia Pac. J. Pharmacol.？1992, 7, 73–82.
[180]
Dilley, J.; Stier, C.; Ardenshorst, W. Abnormalities in glomerular function in rats developing spontaneous hypertension. Am. J. Physiol.？1984, 246, F12–F20. 6696074
[181]
Gellar, R.; Margolius, H.S.; Pisano, J.; Keiser, H.R. Effects of chronic excess salt ingestion. Evidence that genetic factors play an important role in susceptibility to experimental hypertension. Circ. Res.？1975, 36 (Suppl. I.).
[182]
Figueroa, C.D.; Bhoola, K.; Maclever, A.; Mckenzie, J. An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: Comparison with human hypertensive nephropathy. Nephrol. Dial. Transplant.？1992, 7, 516–525. 1320231
[183]
Dahl, L.; Heine, M.; Tassinari, L. Effects of chronic excess salt ingestion. Evidence that genetic factors play an important role in susceptibility to experimental hypertension. J. Exp. Med.？1962, 115, 1173–1190, doi:10.1084/jem.115.6.1173. 13883089
[184]
Dahl, L.; Knudsen, K.; Heine, M.; Leiti, G. Effects of chronic excess salt ingestion. Genetic influence on the development of salt hypertension in parabiotic rats: Evidence for a humoral factor. J. Exp. Med.？1967, 126, 687–699, doi:10.1084/jem.126.4.687. 6058221
[185]
Iwai, J.; Knudsen, K.; Dahl, L.; Heine, M.; Leiti, G. Genetic influence on the development of renal hypertension in parabiotic rats. Evidence for humoral factor. J. Exp. Med.？1969, 129, 507–522, doi:10.1084/jem.129.3.507. 4304137
[186]
Knudsen, K.; Iwai, J.; Heine, M.; Leiti, G.; Dahl, L. Genetic influence on the development of renoprival hypertension in parabioteic rats. Evidence that a humoral hypertensionogenic factor is produced in kidney tissue of hypertension-prone rats. J. Exp. Med.？1969, 130, 1353–1365, doi:10.1084/jem.130.6.1353. 5352784
[187]
Dahl, L.; Heine, M.; Tassinari, L. Effects of chronic excess salt ingestion. Role of genetic factors in both DOCA-salt and renal hypertension. J. Exp. Med.？1963, 118, 605–617, doi:10.1084/jem.118.4.605. 14067908
[188]
Dahl, L.; Heine, M.; Tassinari, L. Effects of chronic excess salt ingestion. Further demonstration that genetic factors influence the development of hypertension; evidence from experimental hypertension due to cortisone and to adrenal regeneration. J. Exp. Med.？1965, 122, 533–545, doi:10.1084/jem.122.3.533. 5839285
[189]
Churchill, P.; Churchill, M.; Bidani, A.; Rabito, S. Kallikrein excretion in Dahl salt–sensitive and salt-resistant rats with native and transplanted kidney. Am. J. Physiol.？1995, 269, F710–717. 7503238
[190]
Arbeit, L.; Serra, S. Decreased total and active urinary kallikrein in normotensive Dahl salt susceptible rats. Kidney Int.？1985, 28, 440–446, doi:10.1038/ki.1985.150. 3851974
[191]
Rapp, J.; Tan, S.; Margolius, H.S. Plasma mineral corticoids, plasma renin, and urinary kallikrein in salt-sensitive and salt-resistant rats. Endocrinol. Res. Comm.？1978, 5, 35–41, doi:10.3109/07435807809073634.
[192]
Sustarsic, D.; McPartland, R.; Rapp, J. Developmental patterns of blood pressure and urinary protein, kallikrein, and prostaglandin E2 in Dahl salt-hypertension-susceptible rats. J. Lab. Clin. Med.？1981, 98, 599–606. 6912875
[193]
Rapp, J.; Joseph, M.; McPartland, R. Proteins binding to kallikrein and esterase A2 in the urine of salt-sensitive and salt-resistant rats. Hypertension？1982, 4, 545–555. 6759395
[194]
McPartland, R.; Rapp, J.; Sustarsic, D. Effects of dexamethasone on excretion of urinary kallikrein and urinary protein in Dahl salt-sensitive and salt-resistant rats. Endocrine Res. Com.？1981, 8, 145–153, doi:10.3109/07435808109045735.
[195]
Rapp, J.; McPartland, R.; Sustarsic, D. Anomalous response of urinary kallikrein to deoxycorticosterone in Dahl salt-sensitive rats. Hypertension？1982, 4, 20–26.
[196]
Rapp, J.; McPartland, R.; Batten, C. Isoelectric focusing patterns of urinary kallikrein in Dahl salt-hypertension susceptible and resistant rats. Hypertension？1984, 6, 519–525. 6378789
[197]
Carretero, O.A.; Polomski, C.; Hampton, A.; Scicli, A.G. Urinary kallikrein, plasma renin and aldosterone in New Zealand genetically hypertensive (GH) rats. Clin. Exp. Pharmacol. Physiol.？1976, 3 (Suppl.), 55–59.
[198]
Gilboa, N.; Rudofsky, U.; Margo, A. Urinary and renal kallikrein in hypertensive fawn-hooded (FH/Wjd) rats. Lab. Invest.？1984, 50, 72–78. 6363817
[199]
Bianchi, G.; Fox, U.; OImbasciati, E. The development of a new strain of spontaneously hypertensive rats. Life Sci.？1974, 14, 339–347, doi:10.1016/0024-3205(74)90064-2. 4813594
[200]
Porcelli, G.; Bianchi, G.; Croxatto, H.R. Urinary kallikrein excretion in a spontaneously hypertensive strain of rats. Proc. Natl. Acad. Sci. USA？1975, 149, 983–986.
[201]
Whelton, P. Potassium and blood pressure. In Hypertension Primer; Wolters Kluwer/Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2008.
[202]
Ito, H.; Majima, M.; Nakajima, S.; Hayashi, I.; Katori, M.; Izumi, T. Effect of prolonged administration of a urinary kininase inhibitor, ebelactone B on the development of deoxycorticosterone acetate-salt hypertension in rats. Br. J. Pharmacol.？1999, 126, 613–620, doi:10.1038/sj.bjp.0702340. 10188971
[203]
Giros, B.; Gros, C.; Schwartz, J.; Danvy, D.; Plaquevent, J.; Duhamel, L.; Duhamel, P.; Vlaiculescu, A.; Costentin, J.; Lecomte, J. Enantiomers of thiorphan and acetorphan: Correlation between enkephalinase inhibitor, protection of endogenous enkaphalins and behavioral affects. J. Pharmacol. Exp. Ther.？1987, 243, 666–673. 3479550
[204]
Lecomte, J.; Baumer, P.; Lim, C.; Duchier, J.; Cournot, A.; Dussaule, J.-C.; Ardaillou, R.; Gros, C.; Chaigon, B.; Souque, A.; Schwartz, J. Steroselective protection of exogenous and endogenous atrial natriuretic factors by enkephalinase inhibitors in mice and humans. Eur. J. Pharmacol.？1990, 170, 65–73, doi:10.1016/0014-2999(90)90402-R.
[205]
Ertl, G.; RA, K.; de Graeff, P.; Kingma, J.; Wesseling, H.; de Langen, C. Captopril reduced purine loss and reperfusion arrhythmias in the rats heart after coronary artery occlusion. Europ. J. Pharmacol.？1984, 100, 113–117, doi:10.1016/0014-2999(84)90323-6.
[206]
Linz, W.; Schoelkens, B.; Han, Y. Beneficial effects of converting enzyme inhibitor, ramipril, in ischemic rat hearts. J. Cardiovasc. Pharmacol.？1986, 8 (Suppl.).
[207]
Sch？lkens, B.; Linz, W.; Konig, W. Effects of the angiotensin converting enzyme inhibitor, ramipril, in isolated ischemic rat heart are abolished by a bradykinin antagonist. J. Hypertens.？1988, 6 (Suppl.), S25–S28.
[208]
Linz, W.; Wiemer, G.; Gohlke, P.; Unger, T.; Sch？lkens, B. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol. Rev.？1995, 47, 25–49. 7784479
[209]
Dendorfer, A.; Wlofrum, S.; Dominiak, P. Pharmacology and cardiovascular implications of the kinin-kallikrein system. Jpn. J. Pharmacol.？1999, 79, 403–426, doi:10.1254/jjp.79.403. 10361880
[210]
Liu, Y.; Yang, V.; Sharov, V.; Sigmon, D.; Sabbath, H.; Carretero, O.A. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats. Hypertension？1996, 27, 7–13. 8591891
[211]
Linz, W.; Wiemer, G.; Schaper, J.; Zimmermann, R.; Nagasawa, K.; Gohlke, P.; Unger, T.; Sch？lkens, B. Angiotensin converting enzyme inhibitors, left ventricular hypertrophy and fibrosis. Mol. Biochem. Parasitol.？1995, 147, 89–97.
[212]
Yayama, K.; Matsuoka, S.; Nagaoka, M.; Shimizu, E.; Takano, M.; Okamoto, H. Down-regulation of bradykinin B2-receptor mRNA in the heart in pressure-overload cardiac hypertrophy in the rats. Biochem. Pharmacol.？2003, 65, 1017–1025, doi:10.1016/S0006-2952(03)00008-X. 12623134
[213]
Pinto, Y.; Bader, M.; Presquero, J.; Tschope, C.; Groningen, E.; van Gilst, W.; Buikema, H. Increased kallikrein expression protects against cardiac ischemia. FASEB J.？2000, 14, 1861–1863. 11023968
[214]
Sch？lkens, B.; Linz, W. Bradykinin-mediated metabolic effects in isolated perfused rat hearts. Agents Actions？1992, 38, 36–42.
[215]
Ito, H.; Hayashi, I.; Izumi, T.; Majima, M. Bradykinin inhibits development of myocardial infarction through B2 receptor signaling by increment of regional blood flow around the ischemic lesion in rats. Br. J. Pharmacol.？2003, 138, 225–233, doi:10.1038/sj.bjp.0705013. 12522094
[216]
Murry, C.; Jennings, R.; Reier, K. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation？1986, 74, 1124–1136. 3769170
[217]
Yellon, D.; Alkhulaifi, A.; Browne, E.; Pugsley, W. Ischemic preconditioning limits infarct size in the rat heart. Cardiovasc. Res.？1992, 26, 983–987, doi:10.1093/cvr/26.10.983. 1486593
[218]
Lawson, C.; Downey, J. Preconditioning: State of the art myocardial protection. Cardiovasc. Res.？1993, 27, 542–550, doi:10.1093/cvr/27.4.542. 8324783
[219]
Linz, W.; Wiemer, G.; Sch？lkens, B. Role of kinins in the pathophysiology of myocardial ischemia. In vitro and in vivo studies. Diabetes？1996, 45, S51–S58. 8529801
[220]
Yayama, K.; Nagaoka, M.; Takano, M.; Okamoto, H. Expression of kininogen, kallikrein and kinin receptors genes by rat cardiomyocytes. Biochim. Biophys. Acta.？2000, 1495, 69–77, doi:10.1016/S0167-4889(99)00154-8. 10634933
[221]
Brew, E.; Mitchel, M.; Rhering, T.; Gamboni-Robertson, F.; McIntyre, R.J.; Harken, A.; Banerrjee, A. Role of bradykinin in cardiac functional protection after global ischemia-reperfusion in rat heart. Am. J. Physiol.？1995, 269, H1370–H1378. 7485570
[222]
Vegh, A.; Szekeres, L.; Parratt, J. Protective role of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products. Cardiovasc. Res.？1990, 24, 1020–1023, doi:10.1093/cvr/24.12.1020. 2129022
[223]
Goto, M.; Liu, Y.; Uang, X.; Ardell, J.; Cohen, M.; Downey, J. Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ. Res.？1995, 77, 611–621. 7641331
[224]
Yang, X.; Liu, Y.; Sccli, G.; Webb, C.; Carretero, O. Role of kinins in the cardioprotective effect of preconditioning: Study of myocardial ischemia/reperfusion injury in B2 kinin receptor knockout mice and kininogen deficient rats. Hypertension？1997, 30, 735–740. 9323015
[225]
Schultz, R.; Post, H.; Vahlhaus, C.; Heusch, G. Ischemic preconditioning in pigs: A graded phenomenon. Its relation to adenosine and bradykinin. Circulation？1998, 98, 1022–1029. 9737523
[226]
Pan, H.-L.; Chen, S.-R.; Scicli, G.; Carretero, O.A. Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning. Am. J. Physiol. Heart Circ. Physiol.？2000, 279, H116–H121. 10899048
[227]
Griol-Charhbili, V.; Messadi-Laribi, E.; Bascands, J.-L.; Heudes, D.; Menton, P.; Giudecelli, J.-F.; Alhenc-Gelas, F.; Richer, C. Role of tissue kallikrein in the cardioprotective effects of ischemic and pharmacological preconditioning in myocardial ischemia. FASEB J.？2005, 19, 1172–1174. 15860541
[228]
Deutsch, E.; Berger, M.; Kussmaul, W.; Hirshfeld, J.J.; Herrmann, H.; Laskey, W. Adaptation to ischemia during percutaneous transluminal coronary angioplastry. Clinical, hemodynamic, and metabolic features. Circulation？1990, 82, 2044–2051. 2242528
[229]
Yellon, D.; Alkhulaifi, A.; pulgsley, W. Preconditioning the human myocardium. Lancet？1993, 342, 276–277, doi:10.1016/0140-6736(93)91819-8. 8101304
[230]
Lessar, M.; Stoddard, M.; Manchikalapudi, S.; Bolli, R. Bradykinin-induced preconditioning in patients undergoing coronary angioplasty. J. Am. Coll. Cardiol.？1999, 34, 639–650, doi:10.1016/S0735-1097(99)00297-1. 10483942
[231]
Sch？lkens, B. Kinins in the cardiovascular system. Immunopharmacology.？1996, 33, 209–2126, doi:10.1016/0162-3109(96)00061-6. 8856152
[232]
Linz, W.; Wiemer, G.; Sch？lkens, B. Beneficial effects of bradykinin on myocardial energy metabolism and infarct size. Am. J. Cardiol.？1997, 80, 118A–123A, doi:10.1016/S0002-9149(97)00466-9. 9293964
[233]
Mclean, P.; Perretti, M.; Ahluwalia, A. Kinin B(1) receptors and cardiovascular system: Regulation of expression and function. Cardiovasc. Res.？2000, 48, 194–210, doi:10.1016/S0008-6363(00)00184-X. 11054467
[234]
Schulz, R.; Cohen, M.; Behrends, M.; Downey, J.; Heusch, G. Signal transduction of ischemic preconditioning. Cardiovasc. Res.？2001, 52, 181–198, doi:10.1016/S0008-6363(01)00384-4. 11684066
[235]
Messadi-Laribi, E.; Griol-Charhbili, V.; Gaies, E.; Vincent, M.; Heudes, D.; Menton, P.; Alhenc-Gelas, F.; Richer, C. Cardioprotection and kallikrein-kinin system in acute myocardial ischemia in mice. Clin. Exp. Pharmacol. Physiol.？2008, 35, 489–493, doi:10.1111/j.1440-1681.2008.04902.x. 18307747
[236]
Chao, J.; Bledsoe, G.; Yin, H.; Chao, L. The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction. Biol. Chem.？2008, 387, 665–675, doi:10.1515/BC.2006.085.
[237]
Stone, O.; Richer, C.; Emanuelli, C.; van Weel, V.; Quax, P.; Katare, R.; Krankel, N.; Campagnolo, P.; Barcelos, L.; Soirgusa, M.; Sla-Newby, G.; Baldessari, D.; Mione, M.; Vincent, M.; Benest, A.; Al Haj Zen, A.; Gonzalez, J.; Bates, D.; Alhenc-Gelas, F.; Madeddu, P. Critical role of tissue kallikrein in vessel formation and maturation: Implications for therapeutic revascularization. Arterioscler. Thromb. Vasc. Biol.？2009, 29, 657–664, doi:10.1161/ATVBAHA.108.182139. 19164804
[238]
Farhy, R.; Carretero, O.; Scicli, A. Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation. Circ. Res.？1993, 72, 1202–1210. 7684331
[239]
Murakami, H.; Yayama, K.; Miao, R.; Wang, C.; Chao, J.; Chao, L. Kallikrein gene delivery inhibits vascular smooth muscle cell growth and neointima formation in the rat artery after balloon angioplasty. Hypertension？1999, 34, 164–170. 10454435
[240]
Emanueli, C.; Bonaria Salis, M.; Figueroa, C.D.; Chao, J.; Chao, L.; Capogrossi, M.; Madeddu, P. Participation of kinins in the captopril-induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse. Br. J. Pharmacol.？2000, 130, 1076–1082, doi:10.1038/sj.bjp.0703388. 10882392
[241]
Kr？nkel, N.; Katare, R.; Siragusa, M.; Barcelps, L.; Cpmpagnolo, P.; Mangialardi, G.; Fortunato, O.; Spinetti, G.; Tran, N.; Zacharowski, K.; Wngelini, G.; Emanueli, C.; Madeddu, P. Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularization potential. Circ. Res.？2008, 103, 1335–1343, doi:10.1161/CIRCRESAHA.108.179952. 18927465
[242]
Hayashi, I.; Amano, H.; Yoshida, S.; Kamata, K.; Inukai, M.; Fujita, T.; Kumagai, Y.; Furudate, S.; Majima, M. Suppressed angiogenesis in kininogen-deficiencies. Lab. Invest.？2002, 82, 871–880. 12118089
[243]
Ishihara, K.; Hayashi, I.; Yamashina, S.; Majima, M. A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors. Jpn. J. Pharmacol.？2001, 87, 318–326, doi:10.1254/jjp.87.318. 11829151
[244]
Ishihara, K.; kamata, M.; Hayashi, I.; Yamashina, S.; Majima, M. Role of bradykinin in vascular permeability and angiogenesis in solid tumor. Int. Immunopharmacol.？2002, 2, 499–509, doi:10.1016/S1567-5769(01)00193-X.
Guo, Y.; Colman, R. Two faces of high-molecular-weight kininogen (HK) in angiogenesis: Bradykinin turns it on and cleaved HK (HKa) turns it off. J. Thromb. Haemost.？2005, 3, 670–676, doi:10.1111/j.1538-7836.2005.01218.x. 15733059
[247]
Wu, Y.; Schmuckler, N.; Bakdash, N.; Yoder, M.; Overall, C.; Coleman, R. Cleaved high molecular weight kininogen inhibits tube formation of endothelial pregenitor cells via suppression of matrix metalloproteinase 2. J. Thromb. Haemost.？2009, 8, 185–193, doi:10.1111/j.1538-7836.2009.03662.x.
[248]
Yao, Y.; Yin, H.; Shen, B.; Smith, R.J.; Liu, Y.; Chao, L.; Chao, J. Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3beta pathway. Circ. Res.？2008, 103, 1335–1343, doi:10.1161/CIRCRESAHA.108.179952. 18927465
[249]
Emanueli, C.; Madeddu, P. Targeting kinin receptors for the treatment of tissue ischemia. Trends Pharmacol. Sci.？2001, 22, 478–484, doi:10.1016/S0165-6147(00)01761-2. 11543876
[250]
Borgono, C.; Diamandis, E. The emerging roles of human kallikreins in cancer. Nat. Rev. Cancer？2004, 4, 876–890, doi:10.1038/nrc1474.
[251]
Madeddu, P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp. Physiol.？2005, 90, 315–326, doi:10.1113/expphysiol.2004.028571. 15778410
[252]
McCrae, K.; Donate, F.; Merkulov, S.; Sun, D.; Qi, X.; Shaw, D. Inhibition of angiogenesis by cleaved high molecular weight kininogen (HKa) and HKa domain 5. Curr. Cancer Drug Targets？2005, 5, 519–528, doi:10.2174/156800905774574039. 16305348
[253]
Chao, J.; Bledsoe, G.; Yin, H.; Chao, L. The tissue kallikrein-kinin system protects against cardiovascular and renal disease and ischemic stroke independently of blood pressure. Biol. Chem.？2006, 387, 665–675, doi:10.1515/BC.2006.085. 16800727
[254]
Westermann, D.; Schulthesis, H.; Tsch？pe, C. New perspective on the tissue kallikrein-kinin system in myocardial infarction: Role of angiogenesis and cardiac regeneration. Int. Immunopharmacol.？2008, 8, 148–154, doi:10.1016/j.intimp.2007.07.022.
[255]
Chao, J.; Chao, L. Kallikrein gene therapy: A new strategy for hypertensive diseases. Immunopharmacology？1997, 36, 229–236, doi:10.1016/S0162-3109(97)00026-X. 9228551
[256]
Chao, J.; Chao, L. Experimental kallikrein gene therapy in hypertension, cardiovascular and renal diseases. Pharmacol. Res.？1997, 35, 517–522, doi:10.1006/phrs.1997.0179. 9356201
[257]
Xiong, W.; Chao, J.; Chao, L. Muscle delivery of human kallikrein gene reduced blood pressure in hypertensive rats. Hypertension？1965, 25, 715–719.
[258]
Chao, J.; Chao, L. Functional analysis of human tissue kallikrein in transgenic mouse models. Hypertension？1996, 27, 491–494. 8613191
[259]
Wang, C.; Chao, L.; Chao, J. Direct gene delivery of human tissue kallikrein reduced blood pressure in spontaneously hypertensive rats. J. Clin. Invest.？1995, 95, 1710–1716, doi:10.1172/JCI117847. 7535795
[260]
Jin, L.; Zhang, J.; Chao, L.; Chao, J. Gene therapy in hypertension: Adenovirus-mediated kallikrein gene delivery in hypertensive rats. Hum. Gene Ther.？1997, 8, 1753–1761, doi:10.1089/hum.1997.8.15-1753.
Chao, J.; Zhang, J.; Lin, K.; Chao, L. Human kallikrein gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive rats. Hum. Gene Ther.？1998, 9, 21–31, doi:10.1089/hum.1998.9.1-21.
[263]
Yayama, K.; Wang, C.; Chao, L.; Chao, J. kallikrein gene delivery attenuates hypertension and cardiac hypertrophy and enhances renal function in Goldblatt hypertensive rats. Hypertension？1998, 31, 1104–1110. 9576121
[264]
Dobrzynski, E.; Yoshida, H.; Chao, J.; Chao, L. Adenovirus-mediated kallikrein gene delivery attenuates hypertension and protect against renal injury in deoxycorticosterone-salt rats. Immunopharmacology？1999, 44, 57–65, doi:10.1016/S0162-3109(99)00121-6. 10604525
[265]
Xia, C.; Bledsoe, G.; Chao, L.; Chao, J. Kallikrein gene transfer reduced renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats. Am. J. Physiol. Renal Physiol.？2005, 289, F622–F631, doi:10.1152/ajprenal.00427.2004. 15886273
[266]
Wolf, W.; Yoshida, H.; Agata, J.; Chao, L.; Chao, J. Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Kidney Int.？2000, 58, 730–739, doi:10.1046/j.1523-1755.2000.00219.x. 10916096
[267]
Yuan, G.; Deng, J.; Wang, T.; Zhao, C.; Xu, X.; Wang, P.; Voltz, J.; Edin, M.; Xiao, X.; Caho, L.; Chao, J.; Zhang, X.; Zeldin, D.; Wang, D. Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phophatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways. Endocrinology？2007, 148, 2016–2026, doi:10.1210/en.2006-0602. 17272402
[268]
Emanueli, C.; Zacheo, A.; Minasi, A.; Chao, J.; Chao, L.; Salis, M.; Stcca, T; Straino, S.; Capogrossi, M.; Madeddu, P. Adenovirus-mediated human tissue kallikrein gene delivery induces angiogenesis in normoperfused skeletal muscle. Arterioscler. Thromb. Vasc. Biol.？2000, 20, 2379–2385. 11073841
[269]
Emanueli, C.; Salis, M.; Pinna, A.; Stacca, T.; Milia, A.; Spano, A.; Chao, J.; Chao, L.; Sciola, L.; Madeddu, P. Prevention of diabetes-induced microangiopathy by human tissue kallikrein gene transfer. Circulation？2002, 106, 993–999, doi:10.1161/01.CIR.0000027104.33206.C8. 12186806
[270]
Chao, J.; Stallone, J.; Liang, Y.; Chen, L.; Wang, D.; Chao, L. Kallistatin is a potent new vasodilator. J. Clin. Invest.？1997, 100, 11–17, doi:10.1172/JCI119502. 9202051
[271]
Chao, J.; Miao, R.; Chen, L.; Chao, L. Novel roles of kallistatin, a specific tissue kallikrein inhibitors, in vascular remodeling. Biol. Chem.？2001, 382, 15–21, doi:10.1515/BC.2001.003. 11258665
[272]
Simson, J.; Wang, J.; Chao, J.; Chao, L. Histopathology of lymphatic tissues in transgenic mice expressing human tissue kallikrein. Lab. Invest.？1994, 71, 680–687. 7967521
