GENDER DIFFERENCES IN THE EXPRESSION OF ENDOTHELIN RECEPTORS IN HUMANSAPHENOUS VEINS IN-VITRO

The contractile response to endothelin-1 (ET-1) appears to be modulate d by the relative density of ETA and ETB receptors. To determine the e ffects of gender on the distribution of ET receptors, we analyzed the endothelin receptor subtypes on membrane fractions prepared from saphe nous vein samples obtained from patients of different genders undergoi ng coronary artery bypass graft surgery. The contractile response to E T-1 in the presence and absence of 1 mu M of the ETA receptor antagoni st BQ-123 was also investigated. Similar studies were repeated with en dothelium-denuded samples to study the role of endothelium-and smooth muscle-derived ETB receptors. Competitive binding experiments were per formed on membrane fractions using [I-125]ET-1 and unlabeled ligands E T-1, ET-3, sarafatoxin 6c and BQ-123. Analysis of the binding data wit h endothelium-intact samples yielded two classes of binding sites in b oth women and men. In women, the maximum binding capacities were 83 +/ - 6 and 97 +/- 10 fmol/mg protein for ETA and ETB receptors, respectiv ely; the corresponding values in men were 618 +/- 121 and 201 +/- 10 f mol/mg protein. In addition, ET-1-induced contractions were 2-fold gre ater in men than in women at high ET-1 concentrations. Competitive bin ding 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 di fferent in men and women, which might be an important factor in the re gulation of the contractile response.