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Vasorelaxant Effect of a Newly Synthesized Dihydropyridine Ethyl Ester (DHPEE) on Rat Thoracic Aorta: Dual Mechanism of Action
Hossein Babaei,Farzaneh Ebrahimi,Javid Shahbazi Mojarrad,Yadollah Azarmi
Advanced Pharmaceutical Bulletin , 2011,
Abstract: Introduction: DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan) with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine). In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. Methods: The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1μM) or KCl (80μM) or Ang II in normal or calcium-free solutions. Results: Concentration–dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right. Conclusion: DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1) in rat aortic smooth muscle.
Vasorelaxant Effect of Sildenafil on Aorta and Pulmonary Artery in Rabbits  [PDF]
Hanefi Ozbek,Beyhan Eryonucu,Niyazi Guler
International Journal of Pharmacology , 2006,
Abstract: This in vitro study was designed to determine the direct vasorelaxant effect of the sildenafil on isolated rabbit pulmonary artery and compare it with the response of isolated rabbit aorta. Endothelium intact aortic and pulmonary artery rings from seven domestic rabbits were suspended in organ chambers containing 15 mL Krebs solution aerated with 95% O2, 5% CO2. In both phenylephrine and potassium chloride (KCl) precontracted vessels, relaxant responses of sildenafil were recorded by strain gauge transducers connected to a polygraph. Sildenafil (10 9 to 3 10 5 M) induced a dose dependent vasodilation of phenylephrine precontracted aorta and pulmonary artery; 55 and 95% relaxations were obtained, respectively, at a concentration of 3 10 5 M. Sildenafil also caused a dose-dependent vasodilation of KCl-precontracted aorta and pulmonary artery, but this vasodilation was significantly lesser. Sildenafil-induced relaxations were higher in pulmonary arteries when compared to aortic rings precontracted with either phenylephrine or KCl. We concluded that sildenafil induces a dose-dependent vasodilation on phenylephrine and KCl-precontracted rabbit aorta and pulmonary artery. This vasodilatory effect is more potent in pulmonary arteries than in aortic rings.
Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta  [PDF]
Fatima Dahboul, Pierre Leroy, Katy Maguin Gate, Ariane Boudier, Caroline Gaucher, Patrick Liminana, Isabelle Lartaud, Alfonso Pompella, Caroline Perrin-Sarrado
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043190
Abstract: S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide (?NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), ?NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free ?NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2±0.5.10?7 M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6±0.2.10?6 M) and acivicin (8.3±0.6.10?7 M), while it decreased with glycylglycine (4.7±0.9.10?8 M). In endothelium-denuded aorta, EC50 for GSNO alone increased to 2.3±0.3.10?6 M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective.
The Vasorelaxant Effects of Anaxagorea luzonensis A. Grey in the Rat Aorta  [PDF]
P. Tep-Areenan,P. Sawasdee
International Journal of Pharmacology , 2011,
Abstract: The aim of the present research was to study vasorelaxant effects of dichloromethane extract of Anaxagorea luzonensis (CH2Cl2-AL) and its underlying mechanisms. CH2Cl2-AL (1-300 μg mL-1) induced concentration-dependent vasorelaxations which were reduced by endothelial denudation, 300 μM NG-nitro-L-arginine methyl ester (L-NAME) and a combination of 10 μM indomethacin and 300 μM L-NAME, but not indomethacin alone. Raising the extracellular KCl concentration to 60 mM inhibited vasorelaxant responses to CH2Cl2-AL in both endothelium-intact and -denuded rings. Moreover, the responses to CH2Cl2-AL were inhibited by 30 μM barium chloride, 2 μM clotrimazole, 10 μM glibenclamide and 10 μM 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), but not 1 mM 4-aminopyridine. Pre-incubation with CH2Cl2-AL (1-100 μg mL-1) inhibited contractions induced by CaCl2 in a Ca2+-free, high KCl buffer. The present findings demonstrate, in the rat isolated aorta, that vasorelaxant responses to CH2Cl2-AL are, in part, mediated via the endothelium and NO-dependent pathways. Moreover, activation of KIR, KCa, KATP channels seems to play a role in CH2Cl2-AL-induced responses. Interestingly, Inhibition of extracellular Ca2+ influx is largely involved in the action of CH2Cl2-AL. The present study provides scientific evidence to support the use of CH2Cl2-AL as a vasodilator agent.
Vasorelaxant Effects of Sildenafil and Verapamil on Isolated Rat Aorta with and without Intact Endothelium  [PDF]
Hanefi Ozbek,Beyhan Eryonucu,Niyazi Guler
International Journal of Pharmacology , 2006,
Abstract: This study was designed to compare vasorelaxant effects of the sildenafil and verapamil on isolated rat aorta. Endothelium intact and denuded aortic rings were suspended in organ chambers. Sildenafil (10-10 to 10-4 M) induced a dose-dependent vasodilation of phenylephrine precontracted aortic rings. Relaxation of endothelium intact and denuded aortic rings caused by 10-4 M sildenafil was about 96 and 79%, respectively. Verapamil (10-10 to 10-4 M) induced a dose-dependent vasodilation of phenylephrine precontracted aortic rings. Relaxation of endothelium intact and denuded aortic rings caused by 10-4 M verapamil was about 99 and 98%, respectively. In the phenylephrine precontracted aortic rings, pD2 values for sildenafil were 4.93±0.59 and 4.11±0.62 in the presence and absence of endothelium, respectively. The pD2 values for verapamil were not different in the presence and absence of endothelium (5.15±1.05 vs 4.96±1.14). Verapamil and sildenafil showed a similar degree of vasorelaxant effect in the intact aortic rings, although there was a significant difference in the degree of relaxation in the absence of endothelium (98 vs 79%). Sildenafil induced both endothelium-dependent and independent vasorelaxation on the aortic rings. Although, there was no significant difference in the degree of relaxation induced by verapamil and sildenafil in aortic rings with intact endothelium, verapamil has more relaxing effect in the denuded aortic rings.
Treatment of traumatic rupture of the thoracic aorta  [PDF]
Davidovi? Lazar,Markovi? Miroslav,?oli? Mom?ilo,Ili? Nikola
Srpski Arhiv za Celokupno Lekarstvo , 2008, DOI: 10.2298/sarh0810498d
Abstract: INTRODUCTION Interest for traumatic thoracic aorta rupture stems from the fact that its number continually increases, and it can be rapidly lethal. OBJECTIVE The aim of this study is to present early and long term results as well as experiences of our team in surgical treatment of traumatic thoracic aorta rupture. METHOD Our retrospective study includes 12 patients with traumatic thoracic aorta rupture treated between 1985 and 2007. There were 10 male and two female patients of average age 30.75 years (18-74). RESULTS In six cases, primary diagnosis was established during the first seven days days after trauma, while in 6 more than one month later. In 11 cases, classical open surgical procedure was performed, while endovascular treatment was used in one patient. Three (25%) patients died, while two (16.6%) had paraplegia. Nine patients (75%) were treated without complications, and are in good condition after a mean follow-up period of 9.7 years (from one month to 22 years). CONCLUSION Surgical treatment requires spinal cord protection to prevent paraplegia, using cardiopulmonary by-pass (three of our cases) or external heparin-bonded shunts (five of our cases). Cardiopulmonary by-pass is followed with lower incidence of paraplegia, however it is not such a good solution for patients with polytrauma because of hemorrhage. The endovascular repair is a safe and feasible procedure in the acute phase, especially because of traumatic shock and polytrauma which contributes to higher mortality rate after open surgery. On the other hand, in chronic postrauamatic aortic rupture, open surgical treatment is connected with a lower mortality rate and good long-term results. There have been no published data about long-term results of endovascular treatment in the chronic phase.
Study on mechanism of vasorelaxatory effect of Vitis vinifera leaf extract in rat aorta
Mohammad Kazem Gharib Naseri,Akbar Heidari
Physiology and Pharmacology , 2006,
Abstract: Introduction: Our previous studies showed that hydroalcoholic extract of leaf of Vitis vinifera relaxes the phenylephrine-induced contraction in rat thoracic aorta. This effect was dependent on endothelial integrity and NO-cGMP system. The vasorelaxant effect of extract was much lesser on KCl-induced contraction. We, therefore, postulated that K+ channels are involved. The main aim of the present study was to determine the type of K+ channels involved in this vasorelaxant effect. Methods: Thoracic aorta with intact endothelium was removed from adult male Wistar rats (170-220g). The aorta was mounted in an organ bath containing Krebs-Henseleit (37 oC, pH 7.4) bubbled with O2. Aortic contractions were recorded isometrically under 1 g resting tension. The aorta endothelium was considered intact if acetylcholine (1 μM) could induce more than 70% aorta relaxation on 1μM phenylephrine-induced contraction. Extract was prepared by maceration method using 70% alcohol and the solvent was then evaporated. Results: The results showed that in the presence of tetraethylammonium (10 mM), the vasorelaxant effect of extract (0.25, 0.5, 1 and 2 mg/ml) was reduced (P<0.001, n=7). In contrast, glibenclamide (1 μM) had no effect. In calcium-free (plus 0.1 mM of EDTA) Krebs-Henseleit solution, the vasorelaxant effect of extract (0.25, 0.5 and 1 mg/ml) was reduced (P<0.0001, n=8). Furthermore, the vasorelaxant effect of extract was unaffected by indomethacin (1 μM). Conclusion: These results suggest that Vitis vinifera leaf hydroalcoholic extract induces relaxation in rat aorta possibly by opening the Ca2+ -operated K+ channels but, not ATP- sensitive K+ channels and extracellular calcium was essential for inducing vasorelaxation by extract. Furthermore, cyclooxigenase was not involved in this vasorelaxant effect.
Transesophageal echocardiaography evaluation of thoracic aorta  [cached]
Nair Hema
Annals of Cardiac Anaesthesia , 2010,
Abstract: Trans-esophageal echocardiaography is a sensitive, minimally invasive, diagnostic tool which gives real time functional image of the aorta. It helps in the diagnosis of pathologies of aorta like atherosclerosis, aneurysm and aortic dissection.
Different patterns of atherosclerotic remodeling in the thoracic and abdominal aorta
Benvenuti, Luiz Alberto;Onishi, Ronaldo Yukinori;Gutierrez, Paulo Sampaio;Higuchi, Maria de Lourdes;
Clinics , 2005, DOI: 10.1590/S1807-59322005000500002
Abstract: purpose: to investigate the relationship between the vascular diameter and the extent and histologic characteristics of atherosclerosis in the thoracic and abdominal aortas of patients who died of atherosclerotic disease. method: we measured the vascular diameter and evaluated the percentage atrophy of the medial layer of the thoracic and abdominal aortas of 19 patients who died due to atherosclerotic disease. the extent of plaques, calcification, ulceration, thrombosis, and the amount of fat in the plaques were evaluated semiquantitatively. results: atherosclerosis was more severe in the abdominal than the thoracic aorta as indicated by the higher sum of the macroscopic scores (p = .02) and the higher percentage atrophy of the medial layer (p < .001). the diameter of the thoracic, but not of the abdominal aorta, correlated with age (r = 0.56; p = .01), plaque score (r = 0.59; p = .008), calcification score (r = 0.749; p < .001), and fat score (r = 0.48; p = .04). multiple linear regression showed that age (p = .06) and calcification score (p = .001) were the parameters with the strongest association to thoracic aorta diameter. conclusion: there are some differences regarding atherosclerosis in the thoracic compared to the abdominal aorta. progressive thoracic aorta atherosclerosis is associated with fat deposition in the plaques, inducing arterial dilation. in the abdominal aorta, atherosclerosis can either have a similar evolution or be associated with less fat deposition in the arterial wall, which would result in more rigidity, hindering compensatory arterial enlargement.
Vasorelaxant effect of Prunus yedoensis bark
Lee Kyungjin,Ham Inhye,Yang Gabsik,Lee Mihwa
BMC Complementary and Alternative Medicine , 2013, DOI: 10.1186/1472-6882-13-31
Abstract: Background Prunus yedoensis Matsum. is used as traditional medicine—‘Yaeng-Pi’ or ‘Hua-Pi’—in Japan and Korea. However, no studies have examined the pharmacological activities of the P. yedoensis bark. Only the antioxidant and antiviral activities of P. yedoensis fruit and the anti-hyperglycaemic effect of P. yedoensis leaf have been investigated. While studying the antihypertensive effects of several medicinal plants, we found that a methanol extract of P. yedoensis bark (MEPY) had distinct vasorelaxant effects on rat aortic rings. Methods The aortic rings were removed from Sprague–Dawley rats and suspended in organ chambers containing 10 ml Krebs-Henseleit solution. The aortic rings were placed between 2 tungsten stirrups and connected to an isometric force transducer. Changes in tension were recorded via isometric transducers connected to a data acquisition system. Results MEPY relaxed the contraction induced by phenylephrine (PE) both in endothelium-intact and endothelium-denuded aortic rings concentration dependently. However, the vasorelaxant effects of MEPY on endothelium-denuded aortic rings were lower than endothelium-intact aortic rings. The vasorelaxant effects of MEPY on endothelium-intact aortic rings were reduced by pre-treatment with l-NAME, methylene blue, or ODQ. However, pre-treatment with indomethacin, atropine, glibenclamide, tetraethylammonium, or 4-aminopyridine had no affection. In addition, MEPY inhibited the contraction induced by extracellular Ca2+ in endothelium-denuded rat thoracic aorta rings pre-contracted by PE (1 μM) or KCl (60 mM) in Ca2+-free solution. Conclusions Our results suggest that MEPY exerts its vasorelaxant effects via the activation of NO formation by means of l-Arg and NO-cGMP pathways and via the blockage of extracellular Ca2+ channels.
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