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Blood pressure and renin-angiotensin system resetting in transgenic rats with elevated plasma Val5-angiotensinogen

Item Type:Article
Title:Blood pressure and renin-angiotensin system resetting in transgenic rats with elevated plasma Val5-angiotensinogen
Creators Name:Bohlender, J. and Bader, M. and Menard, J. and Nussberger, J.
Abstract:OBJECTIVE: Increases in plasma angiotensinogen (Ang-N) due to genetic polymorphisms or pharmacological stimuli like estrogen have been associated with a blood pressure (BP) rise, increased salt sensitivity and cardiovascular risk. The relationship between Ang-N, the resetting of the renin-angiotensin system, and BP still remains unclear. Angiotensin (Ang) II-induced genetic hypertension should respond to lisinopril treatment. METHODS: A new transgenic rat line (TGR) with hepatic overexpression of native (rat) Ang-N was established to study high plasma Ang-N. The transgene contained a mutation producing Val-Ang-II, which was measured separately from nontransgenic Ile-Ang-II in plasma and renal tissue. RESULTS: Male homozygous TGR had increased plasma Ang-N (∼20-fold), systolic BP (DeltaBP + 26 mmHg), renin activity (∼2-fold), renin activity/concentration (∼5-fold), total Ang-II (∼2-fold, kidney 1.7-fold) but decreased plasma renin concentrations (-46%, kidney -85%) and Ile-Ang-I and II (-93%, -94%) vs. controls. Heterozygous TGR exhibited ∼10-fold higher plasma Ang-N and 17 mmHg DeltaBP. Lisinopril decreased their SBP (-23 vs. -13 mmHg in controls), kidney Ang-II/I (∼3-fold vs. ∼2-fold) and Ile-Ang-II (-70 vs. -40%), and increased kidney renin and Ile-Ang-I (>2.5-fold vs. <2.5-fold). Kidney Ang-II remained higher and renin lower in TGR compared with controls. CONCLUSION: High plasma Ang-N increases plasma and kidney Ang-II levels, and amplifies the plasma and renal Ang-II response to a given change in renal renin secretion. This enzyme-kinetic amplification dominates over the Ang-II mediated feedback reduction of renin secretion. High Ang-N levels thus facilitate hypertension via small increases of Ang II and may influence the effectiveness of renin-angiotensin system inhibitors.
Keywords:Angiotensin, Angiotensinogen, Cardiovascular Risk, Gene, Hypertension, Kidney, Transgenic Rat, Animals, Rats
Source:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Page Range:1597-1605
Date:August 2012
Official Publication:https://doi.org/10.1097/HJH.0b013e3283550f76
PubMed:View item in PubMed

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