REDUCTION OF VENTRICULAR M(2) MUSCARINIC RECEPTORS IN CARDIOMYOPATHICHAMSTER (CHF-147) AT THE NECROTIC STAGE OF THE MYOPATHY

We have previously demonstrated that isolated ventricular myocytes fro m cardiomyopathic hamsters (CHF 147) during the necrotic stage (70-100 days) exhibit an attenuated contractile response to muscarinic stimul ation. In the present study we have investigated whether this dysfunct ion may be related to a change in the density (or affinity) of cardiac muscarinic receptors. Thus, we have characterized and quantified the binding of the muscarinic antagonist [H-3]-N-methyl scopolamine (NMS) to M(2) muscarinic receptors in cardiac micropunches and in suspension s of isolated intact cardiomyocytes obtained from cardiomyopathic (CHF 147) and Golden Syrian hamsters. The hamsters were either 70-100 days old, when the cardiomyopathy had reached the cytolytic and necrotic s tage or 30 days old, i.e. before the onset of the cardiomyopathy. In b oth preparations (micropunches and dissociated cardiomyocytes) the spe cific binding of [H-3]-NMS was stereospecific, reversible, saturable, of high affinity and linearly dependent upon increasing amounts of tis sue and cells. The binding site also possessed the drug specificity ty pical of an M(2) muscarinic receptor. Saturation binding analysis reve aled that the hearts of the older CHF 147 hamsters contain significant ly fewer M(2) muscarinic receptors than the control Golden Syrian hams ters while the affinity (K-d) was not altered. This reduction of M(2) receptor number was not observed in CHF 147 hamsters at 30 days. Furth er, we found no differences in beta-adrenergic or in alpha(1)-adrenerg ic binding in the two strains of hamster at either age. Thus, our resu lts indicate that the parasympathetic regulation of cardiac function i n CHF 147 hamsters may be compromised by a decreased number of muscari nic receptors at the necrotic stage of the cardiomyopathy.