RELATIVE ROLES OF NITRIC-OXIDE AND CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS OF ARACHIDONIC-ACID IN THE CONTRACTILE RESPONSES OF RAT RENAL ARCUATE ARTERIES

1 We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate ar teries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitropruss ide. 2 Noradrenaline, potassium chloride and endothelin-1 caused conce ntration-dependent contraction of the vessels. Indomethacin (14 mu M) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following. e ndothelial removal. 3 Acetylcholine produced concentration-dependent r elaxation of the vessels which was potentiated by indomethacin (14 mu M). 4 N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) did not aff ect the contractile response to either noradrenaline or potassium chlo ride but abolished relaxation to acetylcholine. In addition, L-NAME ab olished the affects of indomethacin on acetylcholine-induced relaxatio n and noradrenaline- and potassium chloride-induced contraction. 5 BWC 755C attenuated noradrenaline and potassium chloride-induced contracti on. This effect persisted in the presence of indomethacin. 6 In vessel s pretreated with CHAPS, BW755C inhibited both noradrenaline and potas sium chloride-induced contraction. In these vessels BW755C had no addi tional inhibitory effect to indomethacin on noradrenaline- and potassi um-induced contraction. 7 Inhibition of nitric oxide synthase with L-N AME (100 mu M) attenuated the effect: of BW755C on noradrenaline- and potassium-induced contraction. 8 BW755C alone did not affect endotheli um-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholi ne-induced relaxation.