DIFFERENTIAL-EFFECTS OF SULINDAC ON RENAL HEMODYNAMICS AND FUNCTION IN THE RAT

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 m g/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreas ed (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac g roup (n = 7), renal blood flow progressively and significantly increas ed from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomita nt intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pr essure limits for efficient and no renal blood flow autoregulation rem ained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/ kg b.w, sulindac group (n = 5), renal blood flow did not change but au toregulatory pressure limits were lowered by 10 mmHg 2 h after treatme nt (P < 0.025). Also, Na+ retention was marked. Prostanoid excretion i n urine was significantly reduced with either dose but basal plasma re nin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, diffe rential effects of sulindac on renal hemodynamics, Nai excretion and p lasma renin activity were demonstrated. Renal hemodynamic changes coul d be related in part to the cytochrome P-450 arachidonic acid pathway. (C) 1997 Elsevier Science B.V.