INTERDEPENDENCE OF CONTRACTILE RESPONSES OF RAT SMALL MESENTERIC-ARTERIES ON NITRIC-OXIDE AND CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS OF ARACHIDONIC-ACID

1 We have examined the effects of nitric oxide inhibition, indomethaci n and the dual lipoxygenase/cyclo-oxygenase inhibitor, -amino-1-[m-(tr ifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of smal l mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and so dium nitroprusside. 2 Noradrenaline, potassium chloride and endothelin -1 caused concentration-dependent contraction of small mesenteric arte ries. Indomethacin (14 mu M) attenuated the contractile response to bo th noradrenaline and potassium chloride. The inhibitory action of indo methacin persisted in vessels treated with CHAPS. 3 Acetylcholine prod uced concentration-dependent relaxation in these vessels. Indomethacin (14 mu M) had no significant effect on the acetylcholine concentratio n-response relationship. 4 N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) potentiated the contractile response to both noradrenaline a nd potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5 BW755C inhibited the contractile response to noradrenaline and potassium chloride but not t o endothelin-1. The inhibitory effects of BW755C persisted in the pres ence of indomethacin and in vessels treated with CHAPS. 6 BW755C enhan ced endothelium-dependent relaxation, as assessed by the response to a cetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7 Inhibition of nitric oxide synthase with L-NAME, reversed the inhibito ry effect of BW755C on noradrenaline- and potassium-induced contractio n. L-NAME and BW755C in combination resulted in a shift to the right o f the concentration-response curve to acetylcholine. 8 Sodium nitropru sside produced concentration-dependent relaxation of the vessels. Endo thelium removal reduced the maximum relaxation to nitroprusside. BW755 C did not alter the response to sodium nitroprusside in vessels with o r without endothelium. 9 These data support the existence of two vasoc onstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which app ear to be largely endothelium-independent.