Angiotensdv II type 1 receptor (AT 1) antagonism improves ventricular relaxation after myocardial infarction (MI)

J. Ambrose, G. Giraud, D. Pribnow, L. Muldoon, K. Perkins, B. Greenberg

Research output: Contribution to journalArticle

Abstract

Aims & Methods: Diastolic abnormalities post-Mi have important hemodynamic effects. To assess whether changes in diastolic traction are mediated by Angiotcnsin II(AII), the effect of BMS-186295, a selective AT 1 receptor antagonist was evaluated post-ML Male Sprague Dawley rats were randomized into 4 groups: Sham (SH), Sham + BMS-186295 (SH +BMS), MI and MI + BMS. MI was produced by proximal left anterior descending(LAD) coronary artery tigation. Sham operation was similar but without LAD ligation. Hemodynamics were assessed at 6 weeks and the time constant of isovolumic relaxation(tau), a measure of active diastolic relaxation was measured with a solid state catheter. Results: SH SH + BMS MI MI + BMS Sample size n = 10 n = 5 n = 6 n = 7 Heart wt/Body wt 2.77±0.14 2.43±0.11 3.68 ± 0.56 * 2.81 ± 0.33 ** MAP (mmHg) 120 ± 15 112 ± 11 94 ± 4 * 88 ± 18 LVEDP (mmHg) 7.3 ± 2.9 5.6 ± 2.3 23.3 ± 5.4 * 16.9 ± 10 tau (msec) 20.9 ± 2.8 20.4 ± 1.4 33.6 ± 6.4 * 25.3 ± 6.5 ** * MI vs SH, ** MI vs MI + BMS (p < 0.001) Conclusions: (1) AT 1 antagonism decreased ventricular hypertrophy post MI. (2) Isovolumic relaxation improved post-Mi with AT 1 antagonism independent of significant changes in MAP and LVEDP. (3) AT 1 antagonism did not improve relaxation in sham animals. These findings suggest that the effects of BMS-186295 on LV relaxation post-Mi are unrelated to acute hemodynamic changes and more likely reflect intrinsic alterations in myocyte diastolic Junction.

Original languageEnglish (US)
Pages (from-to)147A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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