| Aldosterone antagonist facilitates the cardioprotective effects of angiotensin receptor blockers in hypertensive rats. | |
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MedLine Citation:
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PMID: 15097243 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: There is increasing evidence to support the importance of blocking aldosterone to prevent target-organ damage in hypertension. We recently demonstrated an aldosterone breakthrough phenomenon during administration of an angiotensin type 1 receptor blocker (ARB). OBJECTIVE: To elucidate the pathophysiological significance of residual aldosterone by investigating the influence of the aldosterone antagonist on the cardioprotective effects of the ARB in hypertensive rats. METHODS: Injection vehicle alone, ARB (1.0 mg/kg per day candesartan by mouth), aldosterone antagonist (10 mg/kg per day spironolactone, subcutaneously), or combined treatment were administered to male stroke-prone spontaneously hypertensive rats for 24 weeks from the age of 4 weeks. Blood pressure, plasma angiotensin II and aldosterone concentrations, left ventricular weight, expression of type I and type III collagen mRNA, and histological findings were determined. RESULTS: In the ARB-treated group, aldosterone concentrations remained unchanged (1.10 +/- 0.20 nmol/l, compared with 1.17 +/- 0.46 nmol/l in the control group), whereas systolic blood pressure (178 +/- 9 mmHg), left ventricular weight (0.372 +/- 0.035 g/100 g body weight), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all decreased significantly compared with the control group (systolic blood pressure: 222 +/- 10 mmHg, P < 0.05; left ventricular weight: 0.483 +/- 0.021 g/100 g body weight, P < 0.05). Although blood pressure (217 +/- 9 mmHg) and left ventricular weight (0.467 +/- 0.027 g/100 g body weight) remained unchanged in the group receiving spironolactone, the expression of both types of collagen mRNA and cardiac interstitial and perivascular fibrosis showed a significant decrease compared with the vehicle-treated group. In the rats receiving combined treatment with the ARB and spironolactone, left ventricular weight (0.352 +/- 0.005 g/100 g body weight, P < 0.05), expression of collagen mRNA, and cardiac interstitial and perivascular fibrosis all showed a further improvement compared with both the ARB and spironolactone groups. CONCLUSIONS: These results demonstrate that residual aldosterone has a significant impact on target-organ damage in hypertension, even during chronic administration of an ARB. The addition of an aldosterone antagonist has an advantage in facilitating the cardioprotective effects of ARBs. |
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Authors:
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Akiyo Tanabe; Mitsuhide Naruse; Yoshiko Hara; Atsuhisa Sato; Ken Tsuchiya; Toshio Nishikawa; Toshihiro Imaki; Kazue Takano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 22 ISSN: 0263-6352 ISO Abbreviation: J. Hypertens. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-04-20 Completed Date: 2004-12-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 1017-23 Citation Subset: IM |
Affiliation:
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Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. akiyotana@endm.twmu.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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blood Aldosterone Antagonists / pharmacology* Angiotensin II / blood Animals Antihypertensive Agents / pharmacology* Benzimidazoles / pharmacology* Body Weight Cardiomegaly / pathology, physiopathology Cardiotonic Agents / pharmacology Collagen Type I / genetics Collagen Type III / genetics Drug Synergism Fibrosis Hypertension / complications, drug therapy*, physiopathology Male Myocardium / pathology RNA, Messenger / analysis Rats Rats, Inbred SHR Rats, Inbred WKY Receptor, Angiotensin, Type 1 / metabolism Spironolactone / pharmacology* Tetrazoles / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Aldosterone Antagonists; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Cardiotonic Agents; 0/Collagen Type I; 0/Collagen Type III; 0/RNA, Messenger; 0/Receptor, Angiotensin, Type 1; 0/Tetrazoles; 11128-99-7/Angiotensin II; 139481-59-7/candesartan; 52-01-7/Spironolactone; 52-39-1/Aldosterone |
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