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

Abstract

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.

Changes in vascular alpha1‐ and alpha2‐adrenoceptor responsiveness by selegiline treatment

“…administration of propranolol hydrochloride (1 mg/kg as a bolus) plus the alpha1‐adrenoceptor antagonist prazosin hydrochloride (0.5 mg/kg as a bolus). The dose of prazosin, chosen according to previous studies [12], is currently used in animal (dog) studies to induce a maximal blockade of alpha‐adrenoceptors. Fifteen minutes later, a dose–response analysis of the pressor responses to noradrenaline (0.5, 1, 2 and 4 μg/kg) was performed in order to assess the responsiveness of vascular alpha2‐adrenoceptors, as previously described [12].…”