Vasomotor effects of various agonists were tested on isolated human epicardial coronary arteries and veins at resting tension and after precontraction with U46619. Acetylcholine relaxed all arteries with intact endothelium but only some endothelium-denuded arteries. Most veins did not relax to acetylcholine. Higher concentrations of acetylcholine induced powerful contractions of all arteries and veins. Preincubation with atropine significantly lowered the pD(2) values but not E(max) values for contractile responses to acetylcholine in arteries and veins (pA(2) value for atropine 9.1 arteries and 9.6 veins). Vasoactive intestinal peptide, human alpha-calcitonin gene-related peptide and substance P potently relaxed all arteries with intact endothelium and all veins. Removal of the arterial endothelium abolished relaxation to substance P in most arteries whereas responses to vasoactive intestinal peptide were unaffected, and for alpha-calcitonin gene-related peptide the pD(2) value but not the E(max) value was significantly lowered. In both arteries and veins, the antagonists alpha-calcitonin gene-related peptide (8-37) and spantide lowered significantly the potency for alpha-calcitonin gene-related peptide and substance P, respectively, without significant changes in E(max) values (pA(2) value for alpha-calcitonin gene-related peptide (8-37) 7.9 arteries and 7.9 veins, for spantide 7.6 arteries and 8.1 veins).