CHANGES IN ELECTROPHYSIOLOGICAL AND MECHANICAL RESPONSES OF THE RAT PAPILLARY-MUSCLE TO ALPHA-AGONIST AND BETA-AGONIST IN STREPTOZOTOCIN-INDUCED DIABETES

To clarify the changes occurring in diabetic animals in the responsive ness of the myocardium to alpha(1)- and beta-adrenoceptor agonists, we examined both alpha- and beta-adrenoceptor-mediated electrophysiologi cal and mechanical responses in the depolarized right ventricular papi llary muscle of streptozotocin (STZ) induced diabetic rats and age-mat ched controls. Both methoxamine (10(-7)-10(-4) M) and isoproterenol (1 0(-9)-10(-6) M) enhanced the slow response action potential in a conce ntration-dependent manner. The amplitude and the APD(50) (time require d for 50% repolarization) of the methoxamine-induced slow response act ion potential were both markedly increased in STZ-induced diabetic rat s in comparison with control rats, whereas those of the isoproterenol- induced slow response were significantly decreased. The methoxamine-in duced contraction in depolarized muscle was slightly but not significa ntly increased in STZ-induced diabetic rats, whereas the isoproterenol -induced contractile response was significantly attenuated. The maximu m number of binding sites (B-max) for [H-3]dihydroalprenolol and for [ H-3]prazosin were both significantly decreased in diabetic rats, compa red with age-matched control rats, without any change in the affinity constants. The slow response action potential induced by methoxamine b ut not isoproterenol was attenuated by IAP (islet-activating factor) t reatment (50 mu g/kg, i.v. for 3 days). These results suggest that an a-adrenoceptor-mediated electrophysiological response is unmasked when the P-adrenoceptor-mediated response is desensitized in the papillary muscle of STZ-induced diabetic rats.