FUROSEMIDE DYNAMICS IN CONSCIOUS RABBITS - MODULATION BY ANGIOTENSIN-II

The aim of this study was to investigate the effects of an infusion of angiotensin II (50 ng/kg/min) on furosemide pharmacodynamics and kine tics in the conscious rabbit. The protocol included a 90-minute phase to estimate the glomerular filtration rate and the renal plasma flow, followed by a 60-minute phase where 5 mg/kg (n = 12) or 10 mg/kg (n = 9) of furosemide were administered. During the pre-furosemide phase, c ompared to control rabbits, angiotensin II increased natriuresis and d iuresis. In the presence of angiotensin II, the furosemide-induced nat riuresis decreased, that is, it was 174 +/- 14 versus 95 +/- 25 mu mol /min (p < 0.05) and 187 +/- 17 versus 89 +/- 21 mu mol/min (p < 0.05) for the 5 and the 10 mg/kg doses, respectively. The infusion of angiot ensin II decreased renal plasma flow without modifying the glomerular filtration rate, thus the filtration fraction was increased. Angiotens in II increased the area under the furosemide plasma concentrations as a function of time since it decreased its systemic clearance. However , furosemide urinary excretion rate was not altered and its renal clea rance decreased slightly without reaching statistical significance. It is concluded that angiotensin II decreases the response to furosemide and the mechanism underlying this effect is related to the pharmacody namics rather than the kinetics of the diuretic.