Role of nitric oxide and cyclooxygenase-2 in regulating the renal hemodynamic response to norepinephrine.
We have reported that the renal hemodynamic effects of norepinephrine (NE) are modulated by cyclooxygenase-2 (COX-2)-derived metabolites. Our main objective was to examine whether there is an interaction between nitric oxide (NO) and COX-2 in modulating the renal hemodynamic effects of NE. NE was infused at three doses to anesthetized dogs pretreated with vehicle (n = 8), a selective COX-2 inhibitor (nimesulide) (n = 6), an NO synthesis inhibitor [NG-nitro-l-arginine methyl ester; l-NAME] (n = 8), or with nimesulide and l-NAME (n = 5). During NE infusion, PGE2 excretion increased (125%) in the control group and did not change in the l-NAME-treated dogs. The simultaneous inhibition of NO and COX-2 potentiated to a greater extent the NE-induced renal vasoconstriction than inhibition of either NO or COX-2. The NE-induced renal vasoconstriction during NO and COX-2 inhibition was reduced (P < 0.05) by infusing an AT1 receptor antagonist (n = 6). These results suggest that there is an interaction between NO and COX-2 in protecting the renal vasculature from the NE effects and that angiotensin II partly mediates the NE-induced renal vasoconstriction when NO synthesis and COX-2 activity are reduced.
López
Ruth
R
Department of Physiology, School of Medicine, University of Murcia, 30100 Murcia, Spain.
Llinas
María T
MT
Roig
Francisco
F
Salazar
F Javier
FJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D007527:Isoenzymes; D013449:Sulfonamides; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C012655:nimesulide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine