Activation of the endothelium-derived relaxing factor system in acute unilateral ureteral obstruction

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.