ALTERATIONS IN CARDIAC ADRENOCEPTORS IN CONGESTIVE-HEART-FAILURE SECONDARY TO MYOCARDIAL-INFARCTION

In order to investigate temporal changes in the status of alpha- and beta-adrenoceptors in hearts failing as a consequence of myocardial infarction, the left coronary artery was ligated in rats and hearts were examined 4, 8, and 16 weeks later; sham-operated age-matched animals served as controls. Clinical signs of congestive heart failure in experimental animals in terms of the presence of lung congestion and cardiac dilatation were evident 8 and 16 weeks following myocardial infarction, whereas abdominal ascites and elevated left ventricular diastolic pressure were observed at 4, 8, and 16 weeks. The density of beta-adrenoceptors in crude membranes, as assessed by [H-3]-dihydroalprenolol binding assay, decreased in the viable left ventricle at 4, 8, and 16 weeks without any change in the affinity of ligand for binding. The density of cardiac alpha-adrenoceptors, as assessed by [H-3]-prazosin binding assay, increased in membrane preparations from experimental animals at 8 and 16 weeks without any change in the binding affinity. Reduction in the beta-adrenoceptor number was also seen in purified sarcolemmal preparations from 4-weeks failing hearts and an increase in the alpha-adrenoceptor number was observed in these preparations from 16-week experimental animals. The functional significance of observed changes in beta- and alpha-adrenoceptors was examined by testing the responses of the isolated perfused hearts to isoproterenol and phenylephrine, respectively. The positive inotropic action due to isoproterenol infusion was depressed at 4 and 8 weeks, whereas the responsiveness to phenylephrine infusion was increased at 8 weeks and unchanged at 4 weeks of occluding the coronary artery. These data support the view that alpha- and beta-adrenergic receptors in the myocardium are altered differently during the development of congestive heart failure subsequent to myocardial infarction. The increase in alpha-adrenoceptor number may serve as an adaptive mechanism, whereas the decrease in beta-adrenoceptor number may explain the attenuated response of the failing heart to catecholamines.