Neural Substrate Essential for Suppression of Vasopressin Secretion and Excretion of a Water Load.

Suppression of vasopressin secretion to very low levels is essential for the excretion of excess water. To investigate a role for the preoptic brain region in the suppression of vasopressin secretion and the excretion of a water load, lesions were made in the vicinity of the lamina terminalis in ewes (LTX-sheep) and responses to water-loading or reduction of cerebrospinal fluid NaCl by i.c.v. isotonic mannitol solution were investigated. In normal conscious sheep, intraruminal water-loading resulted in the urine flow rate increasing and urine osmolality decreasing within 1 h, such that renal free water clearance (CH 2O ) increased from -1.02 ± 0.16 ml/min (mean ± SEM) to a maximum of +4.99 ± 0.62 ml/min at 2.5 h after water-loading (P < 0.05, n = 6). Plasma vasopressin levels fell from 0.88 ± 0.17 pg/ml to undetectable levels (< 0.4 pg/ml, n = 4). In LTX-sheep (n = 6), CH 2O did not change significantly after water-loading (-1.78 ± 0.13 to -2.03 ± 0.49 ml/min at 2.5 h after water-loading). Plasma vasopressin levels were inappropriately elevated in water-loaded LTX-sheep (n = 3). Intracerebroventricular mannitol (1 ml/h for 2 h) resulted in a water diuresis and increase in CH 2O (-1.16 ± 0.12 to +2.81 ± 0.58 ml/min, P < 0.05) after 2 h in normal sheep, and plasma vasopressin levels fell significantly from to 0.88 ± 0.23 pg/ml to < 0.4 pg/ml (P < 0.05, n = 6). However, in LTX-sheep, there was no change in CH 2O (-1.31 ± 0.14 to -1.35 ± 0.12 ml/min) or the plasma vasopressin concentration (1.47 ± 0.18 to 1.60 ± 0.44 pg/ml, not significant) with i.c.v. mannitol. The results suggest that an inhibitory pathway from the vicinity of the median preoptic nucleus to the supraoptic and hypothalamic paraventricular nuclei plays an important role in the suppression of vasopressin secretion and the excretion of excess water.