Regulation of nitric oxide-like activity by prostanoids in smooth muscle of the canine saphenous vein

Abstract

1 Organ bath experiments and measurements of prostanoids were performed to investigate the presence of nitric oxide synthase in venous smooth muscle and its interaction with cyclo-oxygenase. 2 In rings of canine saphenous vein without endothelium, the inhibitor of cyclo-oxygenase, indomethacin (10 μM), induced contraction. N(G)-nitro-L-arginine (100 μM) (L-NOARG), an inhibitor of nitric oxide synthase did not affect the tone of rings of canine saphenous vein when administered alone. However, in the presence of indomethacin L-NOARG (100 μM) induced further contraction. 3 Similar results were obtained in response to N(G)-monomethyl-L-arginine (L-NMMA)(300 μM or N(G)-nitro-L-arginine methylester (L-NAME)(100 μM). 4 When rings of canine saphenous vein without endothelium were contracted with phenylephrine (1 μM) instead of indomethacin, neither L-NOARG or L-NMMA induced further contraction. 5 When rings of canine saphenous vein without endothelium were contracted with noradrenaline (0.3 μM) in the presence of indomethacin (10 μM) plus L-NOARG (100 μM), a relaxation to L-arginine was observed. Transient relaxations to superoxide dismutase (150 u ml-1) were observed in all rings. 6 When rings of saphenous vein without endothelium were incubated with lipopolysaccharide (LPS) (100 μg ml-1) or interleukin -1β (10 u ml-1) the concentration-contraction curve to noradrenaline was not affected. 7 Rings without endothelium released prostaglandin E2 and prostaglandin I2, as measured by radiommunoassay. The basal production was abolished by indomethacin and not affected by L-NOARG. 8 These results suggest that when cyclo-oxygenase is inhibited, a nitric oxide synthase activity is revealed in rings of canine saphenous vein without endothelium.