%0 Journal Article
%T Possible role for nephron©\derived angiotensinogen in angiotensin©\II dependent hypertension
%A Deborah Stuart
%A Donald E. Kohan
%A Fumio Niimura
%A Matias Calquin
%A Nirupama Ramkumar
%A Shuping Wang
%A Taiji Matsusaka
%J Archive of "Physiological Reports".
%D 2016
%R 10.14814/phy2.12675
%X The role of intranephron angiotensinogen (AGT) in blood pressure (BP) regulation is not fully understood. Previous studies showed that proximal tubule©\specific overexpression of AGT increases BP, whereas proximal tubule©\specific deletion of AGT did not alter BP. The latter study may not have completely eliminated nephron AGT production; in addition, BP was only assessed on a normal salt diet. To evaluate this issue in greater detail, we developed mice with inducible nephron©\wide AGT deletion. Mice were generated which were hemizygous for the Pax8©\rtTA and LC©\1 transgenes and homozygous for loxP©\flanked AGT alleles to achieve nephron©\wide AGT disruption after doxycycline induction. Compared to controls, AGT knockout (KO) mice demonstrated markedly reduced renal AGT immunostaining, mRNA, and protein levels; unexpectedly AGT KO mice had reduced AGT mRNA levels in the liver along with 50% reduction in plasma AGT levels. BP was significantly lower in the AGT KO mice compared to controls fed a normal, low, or high Na+ intake, with the highest BP reduction on a low Na+ diet. Regardless of Na+ intake, AGT KO mice had higher plasma renin concentration (PRC) and markedly reduced urinary AGT levels compared to controls. Following angiotensin©\II (Ang©\II) infusion, AGT KO mice demonstrated an attenuated hypertensive response despite similar suppression of PRC in the two groups. Taken together, these data suggest that nephron©\derived AGT may be involved in Ang©\II©\dependent hypertension, however, a clear role for nephron©\derived AGT in physiological BP regulation remains to be determined
%K Angiotensinogen
%K blood pressure
%K kidney
%K liver
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760401/