title: Prostaglandin E2 but not I2 restores furosemide response in indomethacin-treated rats.
abstract: Indomethacin attenuates furosemide's natriuretic response. Although this has been attributed to cyclooxygenase inhibition, attempts to correlate prostaglandin (PG) production with furosemide's natriuresis have led some investigators to conclude that prostaglandins are not involved in this response. This study was designed to evaluate the effects of intraaortic administration of PGE2, PGI2 (100 ng X kg-1 X min-1), or the vasodilators secretin or bradykinin (75 microU X kg-1 X min-1) on the furosemide-indomethacin antagonism. Fractional sodium excretion (FENa) during furosemide administration was 4.59 +/- 0.50% in control rats but 1.84 +/- 0.33% in indomethacin-treated rats (Indo) (P less than 0.001). PGE2 prevented indomethacin from attenuating furosemide's response (FENa, 3.91 +/- 0.25%; P = NS vs. control; P less than 0.01 vs. Indo). PGI2, however, failed to prevent the furosemide-indomethacin antagonism (FeNa, 1.94 +/- 0.59%, P less than 0.001 vs. control; P = NS vs. Indo). Inulin clearance, arterial pressure, filtered sodium load, and renal blood flow were not different between groups. Neither secretin nor bradykinin prevented the indomethacin-furosemide antagonism. This study is consistent with the hypothesis that indomethacin antagonizes furosemide's natriuretic response by prostaglandin synthesis inhibition. Furthermore, PGE2 seems to restore furosemide's response through actions other than a vasodilatory effect.
mesh_terms: D000818:Animals; D004231:Diuresis / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011458:Prostaglandins E; D005665:Furosemide; D011464:Epoprostenol; D007213:Indomethacin