REVERSAL OF THE ANTINATRIURETIC EFFECT OF PROSTAGLANDIN E(2) BY VERAPAMIL IN THE RAT

Previous studies have demonstrated that prostaglandin E(2) (PGE(2)) in fusion increases intrarenal angiotensin-II (ANG-II) formation and decr eases sodium excretion in the rat. PGE(2) infusion may have direct tub ular effects or indirect effects through increased intrarenal ANG-II. In the present study, the calcium channel blocker verapamil was used t o determine whether it would reverse the PGE(2)-induced decrease in so dium excretion. To minimize any systemic and hemodynamic influences, v erapamil and PGE(2) were infused directly into the renal interstitium via a chronically implanted matrix. Fractional sodium excretion (FE(Na )), glomerular filtration rate (GFR), mean arterial pressure (MAP), an d plasma renin activity (PRA) were measured before and during renal in terstitial infusion of PGE(2) (10(-5) M) and/or verapamil (10(-3) M) i n rats pretreated with indomethacin. The renal interstitial infusion o f PGE(2) alone significantly decreased FE(Na) (Delta-1.0+/-0.2%), wher eas the addition of verapamil reversed the effect of PGE, and signific antly increased FE(Na) (Delta 2.6+/-0.3%, n = 9). The renal interstiti al infusion of verapamil alone markedly increased FEN, (Delta 1.7+/-0. 3%, n = 7), and this natriuresis was accompanied by a significant decr ease in PRA (Delta-0.6 +/-0.1 ng/ml/h, p<0.05). The addition of PGE(2) to the interstitial infusion did not further affect FE(Na) or PRA. Th ere was a significant difference between the effect of interstitial PG E(2) infusion and interstitial verapamil infusion on PRA (Delta 1.9+/- 0.8 vs. Delta-0.6+/-0.1 ng/ml/h, p<0.05). GFR and MAP remained unchang ed in response to the renal interstitial infusion of PGE(2) andior ver apamil. In conclusion, verapamil reversed the PGE(2)-induced antinatri uresis in the rat.