EDRF ROLE IN RENAL-FUNCTION AND BLOOD-PRESSURE OF NORMAL RATS AND RATS WITH OBSTRUCTIVE UROPATHY

There is a decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) after release of bilateral ureteral obstruction (BUO) of 24 hours duration. The present studies examine the role of endothelium-derived relaxing factor (EDRF) in the renal hemodynamics of sham-operated rats (SOR) and rats in which BUO of 24 hours duration was unilaterally released. In both groups of rats, renal function and blood pressure were measured in the awake state under basal conditions and after administration of L-arginine (L-arg), the substrate for EDRF synthesis, followed by N(w)NAME, an L-arg antagonist, or after administration of N(w)NAME followed by L-arg. Administration of L-arg alone to SOR did not affect renal function, MAP or RVR. In SOR given L-arg and then N(w)NAME, there was significantly decreased GFR and ERPF and increased MAP and RVR. When N(w)NAME was given initially, similar changes were obtained, and these were reversed by the administration of L-arg. Rats given L-arginine immediately after unilateral release of BUO of 24 hours duration had significantly greater GFR and ERPF values and lower MAP and RVR than temporal controls. N(w)NAME given to BUO rats decreased renal function further and increased MAP and RVR. We found a dose-dependent increase in GFR and ERPF and a dose-dependent decrease in MAP and RVR in both SOR and rats with BUO given increasing amounts of L-arg. There was also a dose-dependent decrease in GFR and ERPF and an increase in MAP and RVR in SOR and rats with BUO given increasing amounts of N(w)NAME or N(G)NMA, the two different antagonists of L-arg. In another set of experiments, SOR and rats with BUO were given L-arg preoperatively (that is, 24 hr prior to study). Both groups of rats had significantly higher GFR and ERPF values and lower MAP and RVR than control rats. Sham-operated rats given N(w)NAME 24 hours prior to study had significantly lower GFR and ERPF and higher MAP and RVR than untreated rats. Rats with BUO given N(w)NAME prior to obstruction had no measurable renal function and had significantly higher values for MAP after release of obstruction. These studies confirm the role of L-arg administration, and presumably EDRF, in the regulation of MAP and renal function in sham-operated rats. The results of this study also suggest decreased availability of arginine for EDRF synthesis in rats with BUO. We suggest that decreased EDRF activity has a role in the renal hemodynamic changes seen following ureteral obstruction.