REGULATION OF BETA-ADRENOCEPTORS IN A RAT MODEL OF CARDIAC-FAILURE - EFFECT OF PERINDOPRIL

This study investigated the effects of myocardial infarction (MI)-indu ced cardiac failure and treatment with an angiotensin-converting enzym e (ACE) inhibitor perindopril (2 mg/kg/day) on rat beta-adrenoceptor ( beta-ar) subtypes in anatomically defined regions of infarcted left ve ntricular (LV) free wall and noninfarcted tissue from right ventricle (RV) by using autoradiography. After 5 weeks of MI, rats with large MI size (>42%) had developed cardiac failure and beta(1)-ars were signif icantly decreased (-59%; p < 0.01) in the border region of the infarct ed LV and almost abolished in the infarcted area (-90%: p < 0.005) com pared with normal LV from sham-operated controls. The beta-ar changes were not found in the noninfarcted area of the same LV or in RV. MI di d not significantly alter the number of beta(2)-ar subtypes in any reg ion of the ventricles. Perindopril treatment for 4 weeks reduced mean cardiac region weights but did not affect beta-ar density in any cardi ac region in either sham-operated or MI rats. These results indicate t hat cardiac failure due to MI causes significant downregulation of bet a(1)-ars only in border and infarcted regions of rat LV and no change in beta-ar in any area. It also suggests that the improved response of the infarcted rat heart to isoprenaline stimulation after ACE inhibit ors does not result from changes in the numbers of cardiac beta-ars.