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The Antagonism of Aldosterone Receptor Prevents the Development of Hypertensive Heart Failure Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats

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Summary

Aldosterone promotes cardiovascular inflammation and remodeling, both of which are characteristic changes in hypertensive and failing hearts. Since chronic inhibition of nitric oxide (NO) synthase with N ω-nitro-L-arginine methyl ester (L-NAME) induces systemic hypertension associated with cardiovascular inflammation and remodeling, we examined the potential role of aldosterone in this process using eplerenone, a selective aldosterone receptor antagonist. Ten-week-old male Wistar-Kyoto rats were randomly divided into 3 groups: the control group (no treatment), the L-NAME group (received L-NAME 1 g/L in drinking water), and the L-NAME+Eplerenone group (L-NAME plus eplerenone at 100 mg/kg/day). After 8 weeks of the treatment, the L-NAME group showed significantly higher systolic blood pressure than the control group (198 ± 7 vs. 141 ± 3 mmHg, P < 0.05). Eplerenone did not affect the increase in blood pressure caused by L-NAME (189 ± 12 mmHg). Chronic inhibition of NO synthesis increased the plasma aldosterone concentration and CYP11B2 mRNA in adrenal glands. Cardiac inflammation and fibrosis were detected in the L-NAME group, while both changes were completely prevented by eplerenone. Cardiac hypertrophy was induced in L-NAME group, but was partially prevented by eplerenone. In the L-NAME group, left ventricular fractional shortening (LVFS: 27 ± 2 vs. 38 ± 1%) and E/A ratio (1.7 ± 0.1 vs. 2.1 ± 0.1) were significantly lower and LV end-diastolic pressure (LVEDP) was higher (4.9 ± 0.6 vs. 13.9 ± 0.5 mmHg) without LV enlargement, compared with those in the control group (P < 0.05). Eplerenone completely normalized LVFS (36 ± 2%), E/A ratio (2.2 ± 0.1), and LVEDP (6.2 ± 0.7 mmHg). These results suggest that chronic inhibition of NO synthesis induces cardiac inflammation and dysfunction via an aldosterone receptor-dependent mechanism.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita Osaka, 565-0871, Japan

    Osamu Tsukamoto, Tetsuo Minamino, Shoji Sanada, Ken-ichiro Okada, Akio Hirata, Masashi Fujita, Yasunori Shintani, Liao Yulin, Yoshihiro Asano, Seiji Takashima & Masatsugu Hori

  2. Departments of Cardiovascular Medicine, National Cardiovascular Center, Suita, 565-8565, Osaka, Japan

    Satoru Yamasaki, Hitonobu Tomoike & Masafumi Kitakaze

  3. MD, PhD, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan

    Tetsuo Minamino

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Correspondence to Tetsuo Minamino.

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Tsukamoto, O., Minamino, T., Sanada, S. et al. The Antagonism of Aldosterone Receptor Prevents the Development of Hypertensive Heart Failure Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats. Cardiovasc Drugs Ther 20, 93–102 (2006). https://doi.org/10.1007/s10557-006-8130-0

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