title: Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats.
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.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamagishi
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Nishikimi
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Takeda
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects; D013777:Tetrazoles
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C077793:candesartan cilexetil; C047759:delapril