| 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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MedLine Citation:
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PMID: 16761190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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(omega)-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:
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Osamu Tsukamoto; Tetsuo Minamino; Shoji Sanada; Ken-ichiro Okada; Akio Hirata; Masashi Fujita; Yasunori Shintani; Liao Yulin; Yoshihiro Asano; Seiji Takashima; Satoru Yamasaki; Hitonobu Tomoike; Masatsugu Hori; Masafumi Kitakaze |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy Volume: 20 ISSN: 0920-3206 ISO Abbreviation: Cardiovasc Drugs Ther Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-06-08 Completed Date: 2006-11-13 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8712220 Medline TA: Cardiovasc Drugs Ther Country: United States |
Other Details:
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Languages: eng Pagination: 93-102 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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drug effects,
metabolism Aldosterone / blood Aldosterone Synthase / genetics, metabolism Animals Blotting, Western Drug Therapy, Combination Fibrosis / drug therapy, pathology, prevention & control Heart Failure / complications, metabolism, prevention & control* Heart Ventricles / drug effects, physiopathology Hypertension / complications, metabolism, prevention & control* Immunohistochemistry Male NF-kappa B / metabolism NG-Nitroarginine Methyl Ester / pharmacology, therapeutic use Nitric Oxide / antagonists & inhibitors*, biosynthesis Peptide Fragments / metabolism Proliferating Cell Nuclear Antigen / analysis Protein Precursors / metabolism RNA, Messenger / genetics, metabolism Random Allocation Rats Rats, Inbred WKY Receptors, Aldosterone / antagonists & inhibitors*, physiology Spironolactone / analogs & derivatives, pharmacology, therapeutic use Transforming Growth Factor beta / metabolism Transforming Growth Factor beta1 |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/NF-kappa B; 0/Peptide Fragments; 0/Proliferating Cell Nuclear Antigen; 0/Protein Precursors; 0/RNA, Messenger; 0/Receptors, Aldosterone; 0/Tgfb1 protein, rat; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/eplerenone; 0/smooth muscle actin, rat; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 52-01-7/Spironolactone; 52-39-1/Aldosterone; EC 1.14.15.4/Aldosterone Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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