The contractile response to endothelin-1 (ET-1) appears to be modulated by the relative density of ETA and ETB receptors. To determine the effects of gender on the distribution of ET receptors, we analyzed the endothelin receptor subtypes on membrane fractions prepared from saphenous vein samples obtained from patients of different genders undergoing coronary artery bypass graft surgery. The contractile response to ET-1 in the presence and absence of 1 microM of the ETA receptor antagonist BQ-123 was also investigated. Similar studies were repeated with endothelium-denuded samples to study the role of endothelium- and smooth muscle-derived ETB receptors. Competitive binding experiments were performed on membrane fractions using [125I]ET-1 and unlabeled ligands ET-1, ET-3, sarafatoxin 6c and BQ-123. Analysis of the binding data with endothelium-intact samples yielded two classes of binding sites in both women and men. In women, the maximum binding capacities were 83 +/- 6 and 97 +/- 10 fmol/mg protein for ETA and ETB receptors, respectively; the corresponding values in men were 618 +/- 121 and 201 +/- 10 fmol/mg protein. In addition, ET-1-induced contractions were 2-fold greater in men than in women at high ET-1 concentrations. Competitive binding studies with endothelium-denuded saphenous veins demonstrated the presence of only ETA receptors in both female and male tissue. These results indicate that the ratio and the density of ET receptors are different in men and women, which might be an important factor in the regulation of the contractile response.