title: Renal Effects of Cyclooxygenase Inhibition When Nitric Oxide Synthesis Is Reduced and Angiotensin II Levels Are Enhanced.
abstract: The involvement of both cyclooxygenase (COX) isoforms in regulating renal function is well known but their interactions with other regulatory mechanisms, such as angiotensin II (Ang II) and nitric oxide (NO), are not well defined. This study has evaluated the relative contribution of both COX isoforms in regulating renal function when NO synthesis is reduced with and without a simultaneous increment in Ang II levels. The renal responses to a nonselective (meclofenamate) or a selective COX2 (nimesulide) inhibitor were examined in dogs pretreated with L-NAME with or without an intrarenal Ang II infusion. Meclofenamate induced a greater (P < 0.05) renal vasoconstriction than nimesulide in dogs pretreated with L-NAME. This vasoconstriction seems to be Ang II-dependent because it was reduced (P < 0.05) by captopril administration. Meclofenamate also induced a greater (P < 0.05) renal vasoconstriction than that elicited by nimesulide in dogs with reduced NO synthesis and elevated Ang II levels. The renal vasoconstriction induced by nimesulide but not that elicited by meclofenamate in dogs pretreated with L-NAME and Ang II, decreased (P < 0.05) during an extracellular volume expansion. These results demonstrate that the nonselective COX inhibition induces a greater renal vasoconstriction than that elicited by the selective COX2 inhibition when NO synthesis is reduced, and when NO synthesis is reduced and Ang II levels are elevated.
authors.affiliation: *Department of Physiology, School of Medicine, Universidad de Murcia; †Regional Campus of International Excellence "Mare Nostrum"; and ‡Instituto Murciano de Investigación Biomédica.
authors.forename: Ruth
authors.initials: R
authors.lastname: López
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Llinás
authors.forename: Elena
authors.initials: E
authors.lastname: Salazar
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Salazar
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008469:Meclofenamic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects* / Q000201:enzymology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D000804:Angiotensin II; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C012655:nimesulide; D019331:NG-Nitroarginine Methyl Ester