Hemodynamic effects of direct angiotensin ii blockade compared to converting enzyme inhibition in rat model of heart failure

Thomas E. Raya, Steven J. Fonken, Richard W. Lee, Sherry Daugherty, Steven Goldman, Pancras C. Wong, Pieter B.M.W.M. Timmermans, Eugene Morkin

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (All) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to All parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril re­duced left ventricular end-diastolic pressure from 26.7 ± 1.5 to 14.2 ± 3.0 (P <.01) and 15.8 ± 2.2 mm Hg(P <.05), respectively, left ventricular end-dia­stolic volume index from 2.71 ± 0.10 to 2.03 ± 0.17 (P <.05) and 2.18 ± 0.15 (P <.05), espectively; ve­nous compliance increased from 2.27 ± 0.06 to 2.80 ± 0.18 (P <.05) and 3.02 ± 0.21 mL/mm Hg/kg (P <.01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduc­tion in total blood volume from 65.8 ±1.1 to 59.4 ± 3.0 and 64.9 ± 3.9 mL/kg, respectively. Thus, direct blockade of All with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. Am J Hypertens 1991;4:334S - 340S.

Original languageEnglish (US)
Pages (from-to)334-340
Number of pages7
JournalAmerican Journal of Hypertension
Volume4
Issue number4
DOIs
StatePublished - Apr 1991
Externally publishedYes

Keywords

  • Afterload reduction
  • Angio­tensin II antagonism
  • Captopril
  • DuP 753
  • Periph­eral circulation
  • Rat heart failure

ASJC Scopus subject areas

  • Internal Medicine

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