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| Item Type: | Article |
|---|---|
| Title: | Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice |
| Creators Name: | Gross, V., Obst, M., Kiss, E., Janke, J., Mazak, I., Shagdarsuren, E., Mueller, D.N., Langenickel, T.H., 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 |
| 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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