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 kinetics 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, compared to control rabbits, angiotensin II increased natriuresis and diuresis. In the presence of angiotensin II, the furosemide-induced natriuresis decreased, that is, it was 174 +/- 14 versus 95 +/- 25 mumol/min (p < 0.05) and 187 +/- 17 versus 89 +/- 21 mumol/min (p < 0.05) for the 5 and the 10 mg/kg doses, respectively. The infusion of angiotensin II decreased renal plasma flow without modifying the glomerular filtration rate, thus the filtration fraction was increased. Angiotensin 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 clearance 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 pharmacodynamics rather than the kinetics of the diuretic.
Homsy
W
W
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Marleau
S
S
du Souich
P
P
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009994:Osmolar Concentration; D011817:Rabbits; D012044:Regression Analysis; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood
D000804:Angiotensin II; D005665:Furosemide; D009320:Atrial Natriuretic Factor; D012083:Renin; D015232:Dinoprostone