EFFECT OF INDOMETHACIN ON THE ADRENAL RESPONSE TO FRUSEMIDE IN THE RAT

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Abstract
Male rats were given 20 mg frusemide (Furantral)/kg body wt, s.c. (or 2 ml 0.9% saline/kg) between 08.40-09.10h. Indomethacin (2.5 mg/kg, s.c.) was administered twice on the day before the experiment and again together with frusemide. Control rats were given 2.5 ml saline/kg (pH 7.4) according to the same schedule. The peripheral aldosterone concentration in 3 untreated rats at 09.00 h was 22, 37 and 57 pg/ml, with corticosterone values < 20 ng/ml. The mean peripheral aldosterone concentration in 5 solvent-treated animals at 12.00 h was 33 .+-. 4 (S.E.M. [standard error of the mean]) pg/ml (corticosterone = 70 .+-. 15 ng/ml). Treatment with indomethacin had no effect on peripheral aldosterone concentration (44 .+-. 6 pg/ml) or corticosterone concentration (81 .+-. 19 ng/ml, n = 5) as measured at 12.00 h. Frusemide evoked a 6-fold increase in mean peripheral aldosterone concentration within 2 h followed by a gradual fall lasting for at least 6 h. Thus acute fluid depletion evoked hyperaldosteronism in the rat as effectively as in other species. The simultaneous increase of corticosterone values indicates a possible contribution of corticotrophin to this reponse albeit the mean corticosterone level was < 200 ng/ml. Pretreatment with indomethacin abolished the increase in peripheral aldosterone concentration 2 h after administration of frusemide. One hour later the effect of indomethacin was less pronounced, although a significant negative interaction (P < 0.025) between frusemide and indomethacin was revealed even at this time by a four-sample modification of the d-test of Behrens and Fisher. No significant changes were observed in plasma Na+ or K+ levels. Basal and frusemide-induced Na and urine excretion rates were reduced by indomethacin, and K+ excretion rate was unaffected.

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