| Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. | |
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MedLine Citation:
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PMID: 9931110 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model. In the present study, we examined whether chronic (2-week) infusion of aldosterone can reverse the renal vascular protective effects of captopril in SHRSP. SHRSP received vehicle (n=8); captopril alone (50 mg. kg-1. d-1, orally) (n=10); aldosterone infusion alone (40 microg. kg-1. d-1, SC) (n=7); or captopril and aldosterone at 20 (n=6) or 40 (n=7) microg. kg-1. d-1. Systolic blood pressure was markedly elevated in all groups. Vehicle- and aldosterone-infused SHRSP developed severe proteinuria and comparable degrees of renal injury (21+/-3% and 29+/-3%, respectively) manifested as thrombotic and proliferative lesions in the arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels concomitant with marked reductions in proteinuria and the absence of histologic lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40 microg. kg-1. d-1 in captopril-treated SHRSP resulted in the development of severe renal lesions (16+/-3% and 21+/-2%, respectively) and proteinuria comparable with that observed in SHRSP given either aldosterone or vehicle alone. These findings support a major role for aldosterone in the development of malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of blood pressure. |
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Authors:
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R Rocha; P N Chander; A Zuckerman; C T Stier |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 33 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1999 Jan |
Date Detail:
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Created Date: 1999-02-26 Completed Date: 1999-02-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 232-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, New York Medical College, Valhalla 10595, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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administration & dosage,
pharmacology* Animals Arterioles / drug effects, pathology* Blood Pressure / drug effects Captopril / pharmacology*, therapeutic use Infusions, Intravenous Kidney Cortex / blood supply*, drug effects, pathology* Kidney Glomerulus / blood supply, drug effects, pathology* Male Proteinuria Rats Rats, Inbred SHR Renal Circulation / drug effects* Sodium, Dietary* |
| Grant Support | |
ID/Acronym/Agency:
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HL-35522/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Sodium, Dietary; 52-39-1/Aldosterone; 62571-86-2/Captopril |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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