The Antagonism of Aldosterone Receptor Prevents the Development of Hypertensive Heart Failure Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats
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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DOI：
10.1007/s10557-006-8130-0
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发表时间：
2006-05
影响因子：
3.4
通讯作者：
O. Tsukamoto;T. Minamino;S. Sanada;K. Okada;A. Hirata;M. Fujita;Y. Shintani;Liao Yulin;Y. Asano;S. Takashima;S. Yamasaki;H. Tomoike;M. Hori;M. Kitakaze
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文献类型：
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作者：
O. Tsukamoto;T. Minamino;S. Sanada;K. Okada;A. Hirata;M. Fujita;Y. Shintani;Liao Yulin;Y. Asano;S. Takashima;S. Yamasaki;H. Tomoike;M. Hori;M. Kitakaze
醛固酮促进心血管炎症和重塑，这两者都是高血压和心脏衰竭的特征性变化。由于用 Nω-硝基-L-精氨酸甲酯 (L-NAME) 慢性抑制一氧化氮 (NO) 合酶会诱发与心血管炎症和重塑相关的全身性高血压，因此我们使用选择性醛固酮受体拮抗剂依普利酮研究了醛固酮在此过程中的潜在作用。十周大的雄性 Wistar-Kyoto 大鼠被随机分为 3 组：对照组（不治疗）、L-NAME 组（在饮用水中接受 1 g/L L-NAME）和 L-NAME+依普利酮组（L-NAME 加依普利酮 100 mg/kg/天）。治疗8周后，L-NAME组的收缩压显着高于对照组（198 ± 7 vs. 141 ± 3 mmHg，P< 0.05）。依普利酮不会影响 L-NAME 引起的血压升高 (189 ± 12 mmHg)。长期抑制 NO 合成会增加血浆醛固酮浓度和肾上腺中 CYP11B2 mRNA。 L-NAME 组检测到心脏炎症和纤维化，而依普利农完全阻止了这两种变化。 L-NAME 组诱导了心脏肥大，但依普利酮部分预防了心脏肥大。与无 LV 扩大的对照组相比，L-NAME 组的左心室缩短分数（LVFS：27 ± 2 vs. 38 ± 1%）和 E/A 比值（1.7 ± 0.1 vs. 2.1 ± 0.1）显着较低，而 LV 舒张末压 (LVEDP) 较高（4.9 ± 0.6 vs. 13.9 ± 0.5 mmHg）。对照组（P<0.05）。依普利酮使 LVFS (36 ± 2%)、E/A 比值 (2.2 ± 0.1) 和 LVEDP (6.2 ± 0.7 mmHg) 完全标准化。这些结果表明，长期抑制 NO 合成会通过醛固酮受体依赖性机制诱导心脏炎症和功能障碍。
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 withNω-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.