Altered vasopressin axis in the AT-1a knockout mouse

The AT1 receptor is involved in the regulation of vasopressin (VP) secretion. The effect of dehydration (2 days) on plasma and posterior pituitary (PP) VP was evaluated in the AT-1a knockout [KO(-/-)] and wild mice [KO(+/+)]. ChgBW P.Osm. P. VP PP VP Group (gram) (mOsm/kg) (pg/ml) (ng) KO(+/+)-W 0.11 ± 0.4 315.8 ± 0.8 17 ± 12 88.5 ± 4.1 KO(+/+)-D -4.21 ± 0.3 348.0 ± 4.9 49 ± 22 59.6 ± 9.8 KO(-/-)-W 0.20 ± 0.4 323.5 ± 8.0 16 ± 3 98.0 ±17.6 KO(-/-)-D -6.03 ± 1.8 388.8 ± 19.9 13 ± 5 37.6 ± 10.6 D=Dehydration, W=Water ad lib, P=Plasma, PP=Posterior Pituitary Basal levels of water intake were elevated in KO(-/-) mice [4.3 ± 03. vs. 6.5 ± 0.5 ml/24 hr; KO(+/+) vs. KO(-/-)]. There was no difference in basal levels of plasma VP and PP VP between groups. There was a greater increase in Osm and greater reduction in BW in the KO (-/-) mice. PP VP was reduced 66% in the KO (-/-) vs 32% in the wild strain. In contrast, plasma VP was increased in the KO (+/+), but not in the KO (-/-). The increased Osm coupled with PP VP depletion suggests that the AT-1a KO is hypersensitive to water restriction. The lack of change in plasma VP may be related to a depletion or fatigue of the neurosecretory system. The data provide support for a role of AT-1a receptors in the regulation of VP secretion and water balance.

Duke Scholars

Author Thomas Myron Coffman Medicine, Nephrology