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

Authors

  • V. Gross
  • M. Obst
  • E. Kiss
  • J. Janke
  • I. Mazak
  • E. Shagdarsuren
  • D.N. Mueller
  • T.H. Langenickel
  • H.J. Groene
  • F.C. Luft

Journal

  • Journal of Hypertension

Citation

  • J Hypertens 22 (5): 997-1005

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.


DOI

doi:10.1097/00004872-200405000-00023