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

Abstract

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 andl-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.