A study of alpha 1- and alpha 2-adrenoceptor responsiveness in diabetic insipidus dogs

The present study was performed to investigate the participation of circulating vasopressin in alpha-adrenoceptor responsiveness. Thus, we compared the pressor responses induced by selective alpha 1-or alpha 2-adrenoceptor stimulation in two groups of conscious dogs: a) normal animals and b) animals with surgically-induced diabetes insipidus. In addition, platelet alpha 2-adrenoceptors labelled with (3H)RX821002 were compared in the two groups. The pressor response to alpha 1-adrenoceptor stimulation [ie successive doses of noradrenaline (0.5, 1, 2, 4 micrograms/kg i.v.) after propranolol (1 mg/kg i.v.) plus yohimbine (0.5 mg/kg i.v.)] was significantly (P < 0.05) less pronounced in diabetic insipidus than in normal dogs. In contrast, the magnitude of the pressor effects of alpha 2-adrenoceptor stimulation [ie noradrenaline after propranolol plus prazosin (1 mg/kg i.v.)] was the same in the two groups of animals. Bmax and Kd values for (3H)RX821002 binding on platelets were similar in diabetic insipidus and normal dogs. This study shows that alpha 1- (but not alpha 2-) adrenoceptor responsiveness is decreased in diabetic insipidus suggesting the involvement of vasopressin in the mechanisms of the vascular alpha 1-adrenoceptor pressor response.