Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle

Jayaseelan Ambrose, David G. Pribnow, George D. Giraud, Keith D. Perkins, Leslie Muldoon, Barry H. Greenberg

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

To evaluate the role of angiotensin II (AII) on diastolic function during post-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental animals were maintained on either irbesartan, a selective AT1 - receptor antagonist, or no treatment. Measurement of cardiac hypertrophy, diastolic function, and sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA) and phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial infarction caused a significant increase in myocardial mass and left ventricular (LV) filling pressure, whereas LV systolic pressure and +dP/dt were reduced. The time constant of isovolumic relaxation (tau) was markedly prolonged after MI. Post-MI hypertrophy was associated with substantial increases in the messenger RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant changes in SERCA or PLB levels. Although irbesartan treatment did not significantly alter post- MI LV systolic or filling pressures, it nevertheless effectively decreased ventricular hypertrophy, improved tau, and normalized ANP expression. These results demonstrate that AT1-receptor antagonism has important effects on myocardial hypertrophy and ANP gene expression, which are independent of ventricular loading conditions. In addition, the improvement in diastolic function was not related to changes in SERCA and PLB gene expression, suggesting that enhanced myocardial relaxation was related to the blockade of AII effects on myocyte function or through a reduction of ventricular hypertrophy itself or both.

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume33
Issue number3
DOIs
StatePublished - Mar 1 1999

Keywords

  • Diastolic function
  • Hypertrophy
  • Irbesartan
  • Myocardial infarction
  • Remodeling
  • SERCA

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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