Relationship between thirst and diazoxide-induced hypotension in rats

Diazoxide, a potent vasodilator and antidiuretic, was used to examine the relationship between hypotension and thirst in conscious rats with indwelling arterial and venous catheters. Bolus iv. injections (5-50 mg/kg) caused prompt, long-lasting, and dose-dependent reductions in mean arterial pressure (MAP) and stimulated drinking. Water intake and degree of hypotension were closely correlated when MAP was 10-65 mmHg below normal. At the time of drinking there were no significant changes in central venous pressure, plasma osmolality, or Na+ or K+ concentration. Plasma glucose increased approximately 35%, and blood volume increased approximately 10% (based on hematocrit changes and dilution of Evans blue). Captopril (100 mg/kg sc to block the renin-angiotensin system) enhanced the depressor response to diazoxide but abolished the dipsogenic response over the same range of arterial pressures tested in controls. Angiotensin II iv infusion restored drinking in captopril-treated animals. The combination of captopril and diazoxide did not block drinking to iv infusions of hypertonic saline or water deprivation. These results confirm that hypotension potently stimulates thirst and support the hypothesis that angiotensin II mediates the dipsogenic response in rats.