Furosemide dynamics in conscious rabbits: modulation by arginine vasopressin

The aims of this study were to assess the influence of arginine-vasopressin (AVP) on the pharmacodynamics and kinetics of furosemide. To this purpose, the response and the kinetics of furosemide (5 mg/kg i.v.) were studied in two groups of rabbits, one control and one receiving an infusion of AVP (2.5 ng/kg/min). The infusion of AVP generated mean plasma levels of 35 pg/ml, and in these rabbits osmolal clearance was increased, free water clearance was reduced, and renal plasma flow was reduced by 25% (p < 0.05). High AVP plasma levels increased the natriuresis (p < 0.01) and the urinary excretion of prostaglandin E2 (UPgE2V; p < 0.01). The increase in UPgE2V was associated with AVP plasma concentrations (r = 0.8248; p < 0.001). AVP reduced the increment in natriuresis and diuresis elicited by furosemide from 163 +/- 20 to 87 +/- 20 mumol/min (p < 0.05) and from 1.22 +/- 0.11 to 0.83 +/- 0.13 ml/min (p < 0.05). The infusion of AVP enhanced furosemide metabolic clearance but diminished its renal clearance, resulting in a decrease in the rate of furosemide urinary secretion. It was concluded that high plasma levels of AVP reduce furosemide natriuresis, presumably because of a decrease in furosemide urinary secretion.