Vasopressin fails to restore postnatally the stunted brain development in the Brattleboro rat, but affects water metabolism permanently.

An attempt was made to prevent the growth impairment of body and brain of the Brattleboro rat congenitally deficient in vasopressin (VP), by postnatal treatment with VP between the ages of 5 and 28 days. Neither repeated daily subcutaneous injections of either Pitressin tannate or VP in oil, continuous peripheral application of VP in various dosage rates using the long-acting Accurel/collodion implantable delivery module, nor daily intracerebroventricular injections of VP in saline, improved postnatal body or brain growth. Brain parts known to be particularly impaired in the Brattleboro neonate, viz. cerebellum and medulla oblongata, also remained unaffected by the VP treatment with regard to both size and cell content as measured on day 33 of age. A possible trophic action of VP would therefore have to take place before neonatal day 5. At dosage rates of VP higher than 1 microgram/d and given peripherally on day 5 or shortly thereafter, a permanent enhancement of diuresis of approximately 30% was noticed in these Brattleboro rats, which were already suffering from a severe diabetes insipidus. Since VP is not circulating at that stage, other systems than the hypothalamo-neurohypophyseal/kidney axis might be affected. Normal antidiuresis obtained following a sub-maximal dosage of Pitressin tannate, indeed showed that the VP receptors of the kidney were still intact. This observation should serve as a warning against application of VP or its analogues during development in clinical practice.