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

R. Saeid Farivar, Dennis C. Crawford, Aram V. Chobanian, Peter Brecher

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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 I 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- · 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 α1-adrenergic and angiotensin type 1 receptors may promote cardiac fibrosis.

Original languageEnglish (US)
Pages (from-to)809-813
Number of pages5
JournalHypertension
Volume25
Issue number4 II
DOIs
StatePublished - Apr 1995

Keywords

  • angiotensin II
  • extracellular matrix
  • fibrosis
  • hypertension, experimental
  • losartan
  • receptors, adrenergic

ASJC Scopus subject areas

  • Internal Medicine

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