Inhibition of ethacrynic acid induced increase in renal blood flow by indomethacin

Abstract

Administration of ethacrynic acid induces, after a delay of 2–3 minutes, an increase in renal blood flow. The delay in onset is also present after renal arterial administration. In order to test the possibility that ethacrynic acid might be releasing vasodilating prostaglandins, indomethacin an inhibitor of prostaglandin synthesis was employed. In six dogs the administration of ethacrynic acid, 0.2 mg/kg, via a renal artery increased renal blood flow by 66 ± 22 ml/min. A second dose administered after indomethacin increased renal blood flow only 8 ± 6 ml/min, a decrease of 58 ml/min. In a second series where indomethacin was not administered, the first dose of ethacrynic acid increased renal blood flow by 65 ± 11 ml/min and 43 ± 8 ml/min after a second administration. Thus while some tachyphylaxis occurs after a second administration, the much greater decrease seen after indomethacin implicates prostaglandins in mediating the renal vasodilation produced by ethacrynic acid.