Distribution of Endothelin Receptors in Saphenous Veins of African Americans: Implications of Racial Differences

The relative density of endothelin-receptor subtypes A and B (ET(A) and ET(B), respectively) on endothelial and smooth muscle cells is the major determinant of the contractile response to endothelin-1 (ET-1). To investigate the effects of race on the distribution of ET receptors, the endothelin-receptor subtypes on membrane fractions prepared from saphenous veins obtained from African-American patients undergoing coronary bypass surgery were analyzed. Similar studies were repeated with endothelium-denuded samples to study the role of endothelium- and smooth muscle-derived ET(B) receptors. Competitive-binding experiments on membrane fractions by using [125I]-ET-1 and unlabeled ligands, ET-1, ET-3, sarafotoxin-6-c, and BQ-123 yielded two classes of binding sites on endothelium-intact vessels from both female and male subjects. In women, the maximal binding capacities were 91+/-6 and 67+/-13 fmol/mg protein for ET(A) and ET(B) receptors, respectively; the corresponding values in men were 178+/-19 and 127+/-13 fmol/mg protein. Similar experiments performed with endothelium-denuded saphenous veins indicated the presence of both receptor subtypes on vascular smooth muscle, in contrast to our earlier report on the presence of only ET(A) receptors on vessels obtained from white Americans. Our findings demonstrate that the ratio and the density of ET receptors are different in black and white Americans.