REGULATION OF NITRIC OXIDE-LIKE ACTIVITY BY PROSTANOIDS IN SMOOTH-MUSCLE OF THE CANINE SAPHENOUS-VEIN

1 Organ bath experiments and measurements of prostanoids were performe d to investigate the presence of nitric oxide synthase in venous smoot h muscle and its interaction with cyclo-oxygenase. 2 In rings of canin e saphenous vein without endothelium, the inhibitor of cyclo-oxygenase , indomethacin (10 mu M), induced contraction. N-G-nitro-L-arginine (1 00 mu M) (L-NOARG), an inhibitor of nitric oxide synthase did not affe ct the tone of rings of canine saphenous vein when administered alone. However, in the presence of indomethacin L-NOARG (100 mu M) induced f urther contraction. 3 Similar results were obtained in response to N-G -monomethyl-L-arginine (L-NMMA)(300 mu M or N-G-nitro-L-arginine methy lester (L-NAME)(100 mu M)). 4 When rings of canine saphenous vein with out endothelium were contracted with phenylephrine (1 mu M) instead of indomethacin, neither L-NOARG or L-NMMA induced further contraction. 5 When rings of canine saphenous vein without endothelium were contrac ted with noradrenaline (0.3 mu M) in the presence of indomethacin (10 mu M) plus L-NOARG (100 mu M), a relaxation to L-arginine was observed . Transient relaxations to superoxide dismutase (150 u ml(-1)) were ob served in all rings. 6 When rings of saphenous vein without endotheliu m were incubated with lipopolysaccharide (LPS) (100 mu g ml(-1)) or in terleukin-1 beta (10 u ml(-1)) the concentration-contraction curve to noradrenaline was not affected. 7 Rings without endothelium released p rostaglandin E(2) and prostaglandin 1(2), as measured by radiommunoass ay. The basal production was abolished by indomethacin and not affecte d by L-NOARG. 8 These results suggest that when cyclo-oxygenase is inh ibited, a nitric oxide synthase activity is revealed in rings of canin e saphenous vein without endothelium.