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Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice

Item Type:Article
Title:Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice
Creators Name:Gross, V. and Obst, M. and Kiss, E. and Janke, J. and Mazak, I. and Shagdarsuren, E. and Mueller, D.N. and Langenickel, T.H. and Groene, H.J. and Luft, F.C.
Abstract:Background: The role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in cardiac hypertrophy and fibrosis is incompletely understood. The availability of AT2 receptor-deficient mice (AT 2 -/y) makes it possible to study the effects of AT1 receptors without the confounding influence of AT2 receptor activity. Objective: To test the hypothesis that the AT2 receptor affords protection from left ventricular hypertrophy and fibrosis in chronic hypertension induced by Nω-nitro-L-arginine methyl ester (L-NAME). Design: Four groups of mice were studied over a period of 3 weeks: AT2 -/y mice with and without L-NAME, and AT2 +/y mice with and without L-NAME. Methods: Blood pressure and heart rate were monitored by telemetry in groups of AT2 +/y and AT2 -/y mice for 4 weeks. L-NAME groups received the compound in drinking water for the last 3 weeks. We determined left ventricular AT1 receptor expression, cardiac hypertrophy and fibrosis, with and without L-NAME treatment. We used a miniaturized conductance-manometer system to measure pressure-volume loops at the time when the animals were killed. Results: AT2 -/y mice treated with L-NAME showed worse left ventricular hypertrophy, more perivascular fibrosis and greater concentrations of brain natriuretic peptide than did AT2 +/y mice treated with L-NAME. The end-systolic pressure-volume relationship, an index of left ventricular contractility, was decreased in AT2 -/y mice treated with L-NAME. Conclusions: The AT2 receptor is not essential for development of L-NAME-induced cardiac hypertrophy, fibrosis and concomitant changes in left ventricular performance. In contrast, the AT2 receptor offers a protective effect.
Keywords:Blood Pressure, Enzyme Inhibitors, Fibrosis, Heart Rate, Hypertension, Left Ventricular Function, Left Ventricular Hypertrophy, Messenger RNA, Mutant Strains Mice, NG-Nitroarginine Methyl Ester, Type 1 Angiotensin Receptor, Type 2 Angiotensin Receptor, Animals, Mice
Source:Journal of Hypertension
ISSN:0263-6352
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:22
Number:5
Page Range:997-1005
Date:May 2004
Official Publication:https://doi.org/10.1097/00004872-200405000-00023
PubMed:View item in PubMed

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