Indomethacin antagonizes furosemide's intratubular effects during loop segment microperfusion

KA Kirchner

Department of Medicine, University of Mississippi Medical Center, Jackson.

To determine if indomethacin antagonizes the effect of intraluminal furosemide, superficial loop segments were microperfused from latest proximal to earliest distal tubules at 20 nl/min with 10(-5) M furosemide in rats treated with indomethacin or vehicle. Base-line loop chloride reabsorption was determined in the presence and absence of indomethacin in a third and fourth group perfused with a similar solution with furosemide omitted. Arterial pressure, whole kidney inulin clearance and urinary chloride excretion were not different among groups. Fractional loop chloride reabsorption was less (P less than .05) in vehicle-treated rats perfused with furosemide than in time control rats perfused without furosemide (30.8 +/- 2.8 vs. 50.3 +/- 2.8%). Fractional chloride reabsorption was greater (P less than .05) in furosemide-perfused loops of indomethacin-treated rats than furosemide-perfused loops of vehicle-treated rats (44.2 +/- 1.9 vs. 30.8 +/- 2.8%). Addition of 10(-4) M prostaglandin E2 to perfusate did not potentiate furosemide's effect in vehicle-treated rats but restored furosemide's potency in indomethacin-treated rats. Thus, indomethacin had no effect on base-line loop chloride uptake but attenuated furosemide's luminal effect. This response could be reversed by luminal prostaglandin E2. This study demonstrates that indomethacin antagonizes furosemide's tubular effects in the absence of furosemide-induced vasodilatation.

Volume 243, Issue 3, pp. 881-886, 12/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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