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

Abstract

. Role of nitric oxide and cyclooxygenase-2 in regulating the renal hemodynamic response to norepinephrine. Am J Physiol Regul Integr Comp Physiol 284: R488-R493, 2003. First published September 19, 2002 10.1152/ajpregu.00449.2002We 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 ϭ 8), a selective COX-2 inhibitor (nimesulide) (n ϭ 6), an NO synthesis inhibitor [N G -nitro-L-arginine methyl ester; L-NAME] (n ϭ 8), or with nimesulide and L-NAME (n ϭ 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 Ͻ 0.05) by infusing an AT 1 receptor antagonist (n ϭ 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 NEinduced renal vasoconstriction when NO synthesis and COX-2 activity are reduced. renal adrenergic system; cyclooxygenases; AT 1 receptors antagonist; kidney THE RENAL VASOCONSTRICTION elicited by norepinephrine (NE) seems to be modulated by nitric oxide (NO) and 12,14,20). The role of PG is supported by studies showing that NE infusion led to an increment in renal PG synthesis (12,14) and that the NE-induced renal vasoconstriction is potentiated when PG synthesis is reduced (6,12,14,20). It has been proposed that the PGs involved in modulating the renal effects of NE are mainly derived from cyclooxygenase-2 (COX-2) (14). The importance of NO has been indicated in studies demonstrating that the renal vasoconstriction elicited by NE is significantly enhanced when NO production is reduced (7,8). On the other hand, it has been suggested that NO enhances COX-2 activity (3,11,24,26). Taking together the studies previously mentioned, it may be proposed that the NE increment in COX-2 activity is mediated by NO. However, it remains to be examined whether this hypothesis is correct.This study evaluates whether NE enhances the production of COX-2-derived metabolites through an NOdependent mechanism and whether the simultaneous inhibition of NO synthesis and COX-2 potentiates the renal hemodynamic effects of NE to a greater extent than the inhibition of either NO synthesis or COX-2 activity. The hypotheses were that 1) NO is involved in the NE-induced increase in COX-2 activity and 2) the simultaneous inhibition of NO synthesis and COX-2 will potentiate more the NE-induced renal vasoconstriction than the inhibition of either NO synthesis or COX-2. If the second hypothesis is correct, t...

Acute Effects of Cyclooxygenase-2 Inhibition on Renal Function in Heterozygous Ren-2-Transgenic Rats on Normal or Low Sodium Intake

“…Indeed, as other investigators [23,26], we demonstrated the efficiency of COX-2 inhibition by showing that intrarenal DuP-697 administration significantly decreased the urinary PGE 2 excretion. The finding that COX-2 inhibition did not alter renal function in HanSD animals fed the NS diet was not surprising, since several previous studies [12,14,21,22] have shown that COX-2 inhibition has no effect on renal function in rats and dogs maintained on a diet with a normal salt content. In addition, Ichihara et al [23] demonstrated that COX-2 inhibition does not influence afferent or efferent arteriolar diameters and does not modulate the afferent arteriolar autoregulatory responses within the kidney under control conditions.…”

Prostaglandins and nitric oxide in regional kidney blood flow responses to renal nerve stimulation

“…In support of this, inhibition of prostaglandin formation enhances, while administration of PGI 2 or PGE 2 blunts, the renal vasoconstrictor response to RNS in anaesthetized rats [14]. There is also considerable evidence for complex interactions between NO and prostaglandins in the kidney [2,3,19,31,32].…”

Shiga toxin-1 affects nitric oxide production by human glomerular endothelial and mesangial cells

“…5). Vasoconstriction will decrease renal blood flow, which supports the accumulation of leukocytes and platelets [26][27][28], which further aggravate glomerular damage. It is of interest to note that the kidney is the main organ involved in the pathogenesis of HUS and the only organ in the human body that contains mesangial cells.…”