Regulation of β-adrenoceptors in a rat model of cardiac failure: Effect of perindopril

This study investigated the effects of myocardial infarction (MI)- induced cardiac failure and treatment with an angiotensin-converting enzyme (ACE) inhibitor perindopril (2 mg/kg/day) on rat β-adrenoceptor (β-ar) subtypes in anatomically defined regions of infarcted left ventricular (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 [β₁-ars were significantly decreased (-59%; p < 0.01) in the border region of the infarcted LV and almost abolished in the infarcted area (-90%; p < 0.005) compared with normal LV from sham-operated controls. The β-ar changes were not found in the noninfarcted area of the same LV or in RV. MI did not significantly alter the number of β₂-at subtypes in any region of the ventricles. Perindopril treatment for 4 weeks reduced mean cardiac region weights but did not affect β-ar density in any cardiac region in either sham-operated or MI rats. These results indicate that cardiac failure due to MI causes significant downregulation of β₁-ars only in border and infarcted regions of rat LV and no change in β₂-at in any area. It also suggests that the improved response of the infarcted rat heart to isoprenaline stimulation after ACE inhibitors does not result from changes in the numbers of cardiac β-ars.