Effect of angiotensin II blockade on the fibroproliferative response to phenylephrine in the rat heart

In this study we infused phenylephrine into adult Wistar rats and used losartan to test for a possible role of angiotensin II in the phenylephrine-induced fibrosis. Phenylephrine, given by Alzet minipumps at a rate of 25 mg.kg-1.d-1, produced a rapid and striking fibrotic response that was obvious a...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1995-04, Vol.25 (4), p.809-813
Main Authors: FARIVAR, R. S, CRAWFORD, D. C, CHOBANIAN, A. V, BRECHER, P
Format: Article
Language:English
Subjects:
Angiotensin II - antagonists & inhibitors
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Animals
Biological and medical sciences
Biphenyl Compounds - pharmacology
Blotting, Northern
Cardiology. Vascular system
Cardiopathies: etiologic forms (general aspects and miscellaneous)
Fibrosis
Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism
Heart
Heart - drug effects
Imidazoles - pharmacology
Indoles - pharmacology
Losartan
Male
Medical sciences
Myocardium - metabolism
Myocardium - pathology
Phenylephrine - pharmacology
Proliferating Cell Nuclear Antigen - metabolism
Rats
Rats, Wistar
Renin-Angiotensin System - physiology
RNA - metabolism
Tetrazoles - pharmacology
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Summary:In this study we infused phenylephrine into adult Wistar rats and used losartan to test for a possible role of angiotensin II in the phenylephrine-induced fibrosis. Phenylephrine, given by Alzet minipumps at a rate of 25 mg.kg-1.d-1, produced a rapid and striking fibrotic response that was obvious after 1 day and progressed throughout a 3-day infusion period. Northern and Western blot analyses showed large increases in cardiac fibronectin expression and atrial natriuretic peptide mRNA, corresponding to fibroblast proliferation and myocyte hypertrophy, respectively. Cardiac fibrosis, fibronectin mRNA, and atrial natriuretic peptide mRNA were blocked by prazosin (7 mg.kg-1.d-1). Administration of losartan (10 mg.kg-1.d-1) resulted in a threefold decrease in interstitial and perivascular fibroblast proliferation, as measured by proliferating cell nuclear antigen immunoreactivity (p < .05), a marked reduction of fibronectin mRNA in the heart, and a moderate reduction of cardiac atrial natriuretic peptide mRNA. The data suggest that effects mediated by a1-adrenergic and angiotensin type 1 receptors may promote cardiac fibrosis.
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.25.4.809