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Occlusion of aortocoronary venous grafts can be due to thrombosis, atherosclerosis, or vasospasm. Investigations have focused on properties of the graft itself, and little is known about the vascular reactivity and function of the native arteries proximal and distal to the vein graft, although spasm of the native artery distal to the graft site has been observed in patients. We hypothesized that the function of the endothelium of the native arteries may be altered after surgery. Autogenous venous grafts were placed in femoral arteries of rabbits to study the reactivity of the native arteries after grafting. Four weeks after graft implantation, the vein graft, ipsilateral vein, and native artery proximal and distal to the graft were removed for in vitro studies. Morphological evaluation by scanning electron microscopy and fluorescence microscopy after labeling with acetylated low density lipoprotein labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate indicated the presence of an intact, metabolically active endothelial layer. There was no alteration in the contractile responses to phenylephrine of the arteries, vein grafts, or veins. Precontracted vein grafts, veins, and arterial segments proximal to the grafts relaxed when exposed to endothelium-dependent vasodilators (acetylcholine, arachidonic acid, and substance P), but the native arteries distal to the grafts did not. In bioassay cascade experiments, the distal artery did not release any measurable relaxing factor when exposed to acetylcholine. We conclude that the endothelium of the distal artery did not function normally. The extent and reversibility of altered endothelial function remain to be determined. This observation may help to explain the occurrence of myocardial infarction after aortocoronary bypass grafting in some patients.