Indomethacin antagonizes furosemide's intratubular effects during loop segment microperfusion.
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.
D000042:Absorption; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D015232:Dinoprostone; D005665:Furosemide / Q000037:antagonists & inhibitors*; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects; D008297:Male; D010477:Perfusion; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D011458:Prostaglandins E; D005665:Furosemide; D015232:Dinoprostone; D007213:Indomethacin