A study of alpha1- and alpha2-adrenoceptor responsiveness in diabetic insipidus dogs

Summary— 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 alpha1-or alpha2-adrenoceptor stimulation in two groups of conscious dogs: a) normal animals and b) animals with surgically-induced diabetes insipidus. In addition, platelet alpha2-adrenoceptors labelled with (³H)RX821002 were compared in the two groups. The pressor response to alpha1-adrenoceptor stimulation [ ie successive doses of noradrenaline (0.5, 1, 2, 4 μg/kg iv) after propranolol (1 mg/kg iv) plus yohimbine (0.5 mg/kg iv)] was significantly ( P < 0.05) less pronounced in diabetic insipidus than in normal dogs. In contrast, the magnitude of the pressor effects of alpha2-adrenoceptor stimulation [ ie noradrenaline after propranolol plus prazosin (1 mg/kg iv)] was the same in the two groups of animals. B_max and Kd values for (³H)RX821002 binding on platelets were similar in diabetic insipidus and normal dogs. This study shows that alpha1- (but not alpha2-) adrenoceptor responsiveness is decreased in diabetic insipidus suggesting the involvement of vasopressin in the mechanisms of the vascular alpha1 -adrenoceptor pressor response.