Urinary excretion and diuretic action of furosemide in rats: increased response to the urinary excretion rate of furosemide in rats with acute renal failure.
A urinary excretion-response curve representing the urinary excretion rate of furosemide versus the urinary excretion rate of (Na+ + K+) was used to analyze furosemide action in rats with uranyl nitrate-induced acute renal failure (ARF) with and without dopamine coadministration. Urinary excretion of furosemide, but not its serum concentration, was the determinant for the diuretic action of furosemide. Increased diuretic response was observed in ARF rats, although the total diuretic response and urinary recovery of furosemide within 2 hr decreased. Dopamine enhanced furosemide-induced diuresis in ARF rats in terms of the total urine output and urinary electrolyte excretion, although the urinary excretion-response curves were not different. This enhancement by dopamine was found to be caused by the augmented urinary excretion of furosemide and the increased response to this drug in ARF rats. These findings suggest the contribution of decreased concentrating ability along the nephron and/or increased sensitivity of cells at the site of action to this drug.
Kikkoji
T
T
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Kamiya
A
A
Inui
K
K
Hori
R
R
D058186:Acute Kidney Injury / Q000652:urine*; D000818:Animals; D004232:Diuretics; D004298:Dopamine / Q000494:pharmacology; D005665:Furosemide / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D005919:Glomerular Filtration Rate; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014502:Uranyl Nitrate / Q000097:blood
D004232:Diuretics; D014502:Uranyl Nitrate; D005665:Furosemide; D004298:Dopamine