Renal medullary adenylate cyclase in rats with hypothalamic diabetes insipidus

The activities of enzymes related to the cellular action of vasopressin as well as the activities of other enzymes were studied in an animal model of hypothalamic diabetes insipidus. Rats with hereditary hypothalamic diabetes insipidus (homozygotes of Bratteboro strain) were found to have significantly lower renal medullary adenylate cyclase activity, either basal activity or activity stimulated by vasopressin, as compared with controls (heterozygotes of the same strain). There were no differences between the two strains in the activities of cyclic AMP phosphodiesterase, other hormone-sensitive adenylate cyclases, or the other renal medullary enzymes studied, which are apparently unrelated to the vasopressin action. The treatment of rats with hereditary hypothalamic diabetes insipidus with exogenous vasopressin increased the activity of renal medullary adenylate cyclase stimulated in vitro by maximal doses of vasopressin, but had no effect on the basal activity of adenylate cyclase or on the activity of cyclic AMP phosphodiesterase. This suggests that low adenylate cyclase activity in the renal medulla of rats with diabetes insipidus may be related to the subnormal concentrating ability observed in these animals.