BETA-ADRENOCEPTORS AND M-CHOLINOCEPTORS IN MYOCARDIUM OF HEARTS WITH CORONARY-ARTERY DISEASE OR IDIOPATHIC DILATED CARDIOMYOPATHY REMOVED AT CARDIAC TRANSPLANTATION

Myocardial force of contraction is regulated by receptors of the autonomic nervous system that are coupled either in a stimulatory or inhibitory way to the adenylate cyclase.1 In the myocardium of patients with heart failure, there is a down-regulation of cardiac β adrenoceptors2 with a reduction of the positive inotropic effects of β-adrenoceptor agonists and phosphodiesterase inhibitors.3 However, little is known about inhibitory receptors such as muscarinic M2-receptors, which couple to the inhibitory-guanine-nucleotide binding protein Gi and reduce force of contraction in the presence of β-adrenoceptor stimulation.4 Since Gi has been reported to be increased in the failing human myocardium,5,6 it is not unreasonable that these receptors could be coregulated with Gi. This would result in increased effects mediated by inhibitory M2-receptor, which would contribute to the reduced response to cyclic adenosine monophosphate (cAMP)-dependent positive inotropic agents. Therefore, the number of myocardial β adrenoceptors and m-cholinoceptors were studied with radioligand binding techniques in explanted human hearts from patients undergoing cardiac transplantation because of severe heart failure (dilated cardiomyopathy, coronary heart disease) and in nonfailing donor hearts that could not be transplanted for technical reasons. The density and antagonist affinity of both β adrenoceptors and m-cholinoceptors were studied in the very same hearts and were correlated to the hemodynamic data obtained from patients before the operations. © 1990.