Changes in electrophysiological and mechanical responses of the rat papillary muscle to alpha- and beta-agonist in streptozotocin-induced diabetes.
To clarify the changes occurring in diabetic animals in the responsiveness of the myocardium to alpha 1- and beta-adrenoceptor agonists, we examined both alpha- and beta-adrenoceptor-mediated electrophysiological and mechanical responses in the depolarized right ventricular papillary muscle of streptozotocin (STZ) induced diabetic rats and age-matched controls. Both methoxamine (10(-7)-10(-4) M) and isoproterenol (10(-9)-10(-6) M) enhanced the slow response action potential in a concentration-department manner. The amplitude and the APD50 (time required for 50% repolarization) of the methoxamine-induced slow response action potential were both markedly increased in STZ-induced diabetic rats in comparison with control rats, whereas those of the isoproterenol-induced slow response were significantly decreased. The methoxamine-induced contraction in depolarized muscle was slightly but not significantly increased in STZ-induced diabetic rats, whereas the isoproterenol-induced contractile response was significantly attenuated. The maximum number of binding sites (Bmax) for [3H]dihydroalprenolol and for [3H]prazosin were both significantly decreased in diabetic rats, compared with age-matched control rats, without any change in the affinity constants. The slow response action potential induced by methoxamine but not isoproterenol was attenuated by IAP (islet-activating factor) treatment (50 micrograms/kg, i.v. for 3 days). These results suggest that an alpha-adrenoceptor-mediated electrophysiological response is unmasked when the beta-adrenoceptor-mediated response is desensitized in the papillary muscle of STZ-induced diabetic rats.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Satoh
T
T
Tanaka
H
H
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008729:Methoxamine; D007545:Isoproterenol