Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats

J Mol Cell Cardiol. 1993 Nov;25(11):1369-80. doi: 10.1006/jmcc.1993.1149.

Abstract

To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynamics and ventricular angiotensin II contents in myocardial-infarcted rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right and left ventricular weight, left ventricular end-diastolic pressure and volume of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor-mediated action of angiotensin II plays a central role in the development of ventricular dilatation. Angiotensin II contents in the right and non-infarcted left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/- S.E.M.) of myocardial-infarcted rats were not different from those of sham-operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/- 3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%, respectively, but did not reduce plasma angiotensin II in myocardial-infarcted rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by 4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was associated with the decrease in ventricular angiotensin II contents. These observations suggest that the cardiac renin-angiotensin system rather than the circulating system may play an important role in ventricular dilatation after myocardial infarction.

MeSH terms

  • Analysis of Variance
  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Benzimidazoles / pharmacology
  • Biphenyl Compounds / pharmacology
  • Hemodynamics / drug effects
  • Indans / pharmacology
  • Male
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Rats
  • Rats, Wistar
  • Receptors, Angiotensin / drug effects
  • Tetrazoles*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Biphenyl Compounds
  • Indans
  • Receptors, Angiotensin
  • Tetrazoles
  • Angiotensin II
  • candesartan cilexetil
  • delapril