Role of cyclooxygenase-2-derived metabolites and nitric oxide in regulating renal function

The aim of this study was to examine the relative contribution of both cycl ooxygenase (COX) isoforms in producing the prostaglandins (PG) involved in the regulation of renal function, when nitric oxide (NO) synthesis is reduc ed. In anesthetized dogs with reduction of NO synthesis, the renal effects of a nonisozyme-specific COX inhibitor (meclofenamate) were compared with t hose elicited by a selective COX-2 inhibitor (nimesulide) before and during an extracellular volume expansion (ECVE). Intrarenal N-G-nitro-L-arginine methyl ester (L-NAME) infusion (1 mug.kg(-1).min(-1); n = 6) did not elicit renal hemodynamic changes and reduced (P < 0.01) the renal excretory respo nse to ECVE. Intravenous nimesulide (5 <mu>g.kg(-1).min(-1); n = 6) did not modify renal hemodynamic and reduced (P < 0.05) sodium excretion before EC VE. Simultaneous L-NAME and nimesulide infusion (n = 7) elicited an increme nt (37%) in renal vascular resistance (RVR; P < 0.05) before ECVE and no he modynamic changes during ECVE. The reduced excretory response elicited by L -NAME and nimesulide was similar to that found during L-NAME infusion. Fina lly, simultaneous L-NAME and meclofenamate infusion (10 mug.kg(-1).min(-1); n = 7) induced an increase in RVR (91%, P < 0.05), a decrease in glomerula r filtration rate (35%, P < 0.05), and a reduction of the renal excretory r esponse to ECVE that was greater (P < 0.05) than that elicited by L-NAME al one. The results obtained support the notion that PG involved in regulating renal hemodynamic and excretory function when NO synthesis is reduced are mainly dependent on COX-1 activity.