Activation of the Endothelium-Derived Relaxing Factor System in Acute Unilateral Ureteral Obstruction

Abstract

Purpose To investigate the effects of L-arginine, a substrate for nitric oxide (NO) synthase, on renal hemodynamics in acute ureteral obstruction (UUO). Materials and Methods Renal blood flow (RBF) and ureteral pressure (UP) were measured in anesthetized dogs with or without UUO. Results In 9 dogs (Group 1), RBF was 212 +/− 13 ml./min. before UUO, and significantly increased to 302 +/− 18 and 268 +/− 9 ml./min. at 90 and 140 min. post-UUO, respectively, associated with a marked increase in UP from 3 +/− 1 mm. Hg to 73 +/− 5 and 83 +/− 2 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs (Group 2) prostaglandin synthesis was inhibited with meclofenamate (5 mg./kg., i.v.). After UUO, RBF did not change significantly and the increase in UP was markedly attenuated when compared with Group 1, as UP rose only to 27 +/− 3 and 34 +/− 4 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs pre-treated with meclofenamate, L-arginine was infused into the renal artery at 5 mg./kg./min. at 90 min. after UUO (Group 3). Prostaglandin synthesis inhibition prevented renal vasodilation after UUO and significantly attenuated the increase in UP. Upon infusion of L-arginine, RBF and UP rose sharply from 202 +/− 16 ml./min. and 24 +/− 6 mm. Hg to 264 +/− 22 ml./min. and 70 +/− 4 mm. Hg, respectively, at 140 min. post-UUO (p <0.001), values approaching those in Group 1. In sham-operated dogs, L-arginine infusion did not alter RBF in dogs with or without pretreatment with meclofenamate. Conclusion In UUO the L-arginine-NO pathway is activated, contributing to renal vasodilation and a marked increase in UP.