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 cyclooxygenase (COX) isoforms in producing the prostaglandins (PG) involved in the regulation of renal function, when nitric oxide (NO) synthesis is reduced. In anesthetized dogs with reduction of NO synthesis, the renal effects of a nonisozyme-specific COX inhibitor (meclofenamate) were compared with those 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 microg x kg(-1) x min(-1); n = 6) did not elicit renal hemodynamic changes and reduced (P < 0.01) the renal excretory response to ECVE. Intravenous nimesulide (5 microg x kg(-1) x min(-1); n = 6) did not modify renal hemodynamic and reduced (P < 0. 05) sodium excretion before ECVE. Simultaneous L-NAME and nimesulide infusion (n = 7) elicited an increment (37%) in renal vascular resistance (RVR; P < 0.05) before ECVE and no hemodynamic changes during ECVE. The reduced excretory response elicited by L-NAME and nimesulide was similar to that found during L-NAME infusion. Finally, simultaneous L-NAME and meclofenamate infusion (10 microg x kg(-1) x min(-1); n = 7) induced an increase in RVR (91%, P < 0.05), a decrease in glomerular filtration rate (35%, P < 0.05), and a reduction of the renal excretory response to ECVE that was greater (P < 0.05) than that elicited by L-NAME alone. 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.
Llinás
M T
MT
Department of Physiology, School of Medicine, University of Murcia, 30100 Murcia, Spain.
Rodríguez
F
F
Moreno
C
C
Salazar
F J
FJ
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011453:Prostaglandins; D013449:Sulfonamides; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide; D019331:NG-Nitroarginine Methyl Ester