Chronic physiological increases in cortisol inhibit the vasopressin response to hypertonicity in conscious dogs

Chronic increases in cortisol inhibit basal plasma arginine vasopressin (AVP). Acute pretreatment with cortisol inhibits the large increase in AVP during hypotension or hypoxia but does not inhibit the modest increase in AVP in response to hypertonic saline (HS). We evaluated the effect of a chronic increase in cortisol (physiological range) on the acute AVP response to HS. Five male dogs received a continuous infusion of either vehicle or cortisol (65 mg/day) for 7 days. The AVP response to HS (0.2 mmol.kg-1.min-1 for 30 min) was tested before infusion, on days 1, 4, and 7 of chronic infusion, and 2 days after the infusion was discontinued. Plasma cortisol increased significantly from 1.0 +/- 0.2 micrograms/dl to an average over the 7 days of infusion of 5.0 +/- 0.2 micrograms/dl, and basal plasma AVP was significantly decreased during cortisol infusion. The increase in plasma Na and osmolality during HS was unaffected by chronic infusion. HS resulted in an increase in AVP from 3.5 +/- 0.2 to 7.1 +/- 0.7 pg/ml before cortisol infusion. After 7 days of cortisol, the AVP response to HS (from 2.6 +/- 0.1 to 3.9 +/- 0.7 pg/ml) was significantly attenuated. Sustained, physiological increases in cortisol significantly inhibited osmotically stimulated AVP release. The decrease in AVP during hypercortisolism and the syndrome of inappropriate antidiuretic hormone in patients with adrenal insufficiency appear to be due to an inhibitory effect of cortisol on the osmotic sensitivity of the AVP control system.