Cyclooxygenase-2 products compensate for inhibition of nitric oxide regulation of renal perfusion.

Cyclooxygenase (COX)-2 is in the macula densa, cosegregating with neuronal nitric oxide synthase (nNOS). It is hypothesized that in response to acute inhibition of NOS, the influence of COX-2-derived prostanoids is exaggerated, compensating for renal vasoconstriction. Blood pressure (BP) and renal blood flow (RBF) were measured after selective COX-2 inhibition with NS-398 followed by NOS inhibition with L-nitro arginine methyl ester (L-NAME) or after L-NAME followed by NS-398. BP was 106 +/- 4 mmHg and was unaffected by NS-398. L-NAME after NS-398 increased BP by 27 +/- 2 mmHg, decreased RBF by one-half, and doubled renal vascular resistance (RVR; P < 0.001). Initial L-NAME increased BP by 26 +/- 3 mmHg (P < 0.001) and decreased RBF by 44% (P < 0.001), doubling RVR. After L-NAME, NS-398 induced a further 7 +/- 3-mmHg rise in BP (P < 0.05), decreased RBF by 20% (P < 0.025), and increased RVR by 23% (P < 0.01). The constrictor response to COX-2 inhibition after L-NAME could not be duplicated by either selective nNOS inhibition or NOS-independent renal vasoconstriction. Acute NOS inhibition unmasked renal vasoconstriction with COX-2 inhibition, suggesting that the influence of COX-2-derived vasodilator eicosanoids is exaggerated to maintain renal perfusion, compensating for the acute loss of NO.