An angiotensin II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat.
OBJECTIVE
The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether the angiotensin II type 1 receptor antagonist (AIIA), TCV-116, prevented left ventricular dilatation after myocardial infarction; and (4) to compare the effect of AIIA with that of the angiotensin converting enzyme (ACE) inhibitor, delapril.


METHODS
Myocardial infarction was produced in SHR and WKY by coronary artery ligation. Haemodynamic measurements were obtained three weeks later in rats that had been treated from the next day after the operation for three weeks with TCV-116 (1 mg.kg-1.d-1) or delapril (1 g.litre-1 in drinking water), and in untreated controls.


RESULTS
After myocardial infarction, left ventricular weight, and left ventricular weight were greater in SHR than in normotensive rats. Right ventricular weight, left ventricular end diastolic pressure, and LVEDVI correlated positively with infarct size in both SHR and WKY and these slopes were steeper in SHR than in WKY (P < 0.05). TCV-116 and delapril each significantly attenuated the increases in left ventricular end diastolic pressure, left ventricular weight, right ventricular weight, and LVEDVI following myocardial infarction in both in WKY and SHR, and shifted pressure-volume curve significantly to the left.


CONCLUSIONS
Hypertension accelerates left ventricular dilatation and haemodynamic alterations following myocardial infarction in rats. These effects are attenuated by an angiotensin II type 1 receptor antagonist as well as by an ACE inhibitor.
Nishikimi
T
T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Yamagishi
H
H
Takeuchi
K
K
Takeda
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D007189:Indans / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D013777:Tetrazoles; C077793:candesartan cilexetil; C047759:delapril