Role of nitric oxide and cyclooxygenase-2 in regulating the renal hemodynamic response to norepinephrine

Department of Physiology, School of Medicine, University of Murcia, 30100 Murcia, Spain 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 [ N G -nitro- L -arginine methyl ester; L -NAME] ( n = 8), or with nimesulide and L -NAME ( n = 5). During NE infusion, PGE 2 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