Impaired Response to Vasopressin of Adenylate Cyclase of the Thick Ascending Limb of Henle’s Loop in Brattleboro Rats with Diabetes insipidus

Abstract

Brattleboro rats with diabetes insipidus (DI) exhibit an impaired urinary concentrating ability in response to exogenous vasopressin (AVP) and a decreased AVP-sensitive adenylate cyclase (AC) in homogenates of kidney medulla. To further analyze this phenomenon, AC responses to AVP were measured in medullary segments of the thick ascending limb of Henle’s loop (MAL) and the collecting tubule (MCT), microdissected from DI and control rats of the same strain. AVP dose-response curves determined in MCT from DI and control rats were identical, indicating that, in that nephron segment, the enzyme response to the hormone was normal in DI rats. In contrast, AC activities measured simultaneously in MAL were on the average 50% lower (p, < 0.001) in DI than in control rats for all AVP concentrations tested. The apparent affinity constant of enzyme activation by the hormone was similar in both groups of animals. These results suggest that the concentrating defect of DI rats in the presence of AVP could result from a subnormal AC responsiveness to AVP selectively affecting MAL.