Detection of intraluminal release of endothelium-derived relaxing factor from human saphenous veins

Background. Most prior physiological studies of the endothelium of intact saphenous veins have used organ chambers to assay abluminal release of vasoactive factors that affect smooth muscle contraction and relaxation. However, intraluminal release of vasoactive factors may have important implications in saphenous vein bypass graft patency. Methods and Results. To study the basal and stimulated intraluminal release of endothelium-dependent relaxing factor (EDRF), 5-cm segments of human saphenous veins were cannulated and perfused in vitro with physiological salt solution. Vasoactive properties of the effluent were bioassayed on canine coronary artery smooth muscle. Effluent from saphenous veins produced vasodilation of 4.0±1.8% (±SEM) (n=26) under basal conditions and 36.1±6.7% when stimulated with calcium ionophore, A23187 (n=19, P<.05). Fourteen of the 26 vein segments showed no basal release of EDRF. Vasodilation produced by the effluent could be eliminated by mechanically removing the endothelium or by treatment with N^G-monomethyl-L-arginine or N^G-nitro-L-arginine, two competitive inhibitors of nitric oxide synthesis from L-arginine. Vasodilation was not influenced by indomethacin. Conclusions. Previous studies of EDRF from human saphenous veins were performed in organ chambers, which could detect only extraluminal EDRF release. This is the first demonstration of intraluminal release of EDRF from human saphenous veins. The variable and relatively poor basal release of EDRF into the lumen may account for early thrombogenicity of vein grafts and may contribute to late atherosclerosis.