Saphenous vein endothelin system expression and activity in African American patients

Objective - Plasma endothelin (ET)-1 levels are significantly higher in African American hypertensive patients than in white hypertensive patients. However, whether the molecular components of vascular ET-1 biosynthesis and function are altered in this population remains to be established. Accordingly, the overall goal of this study was to investigate the effects of race on vascular mRNA and protein levels of ET-converting enzyme (ECE)-1 subisoforms, ET-1, and ET receptor profiles in hypertension. Methods and Results - Saphenous vein samples were obtained from African American (n = 13) and white (n = 15) patients undergoing coronary artery grafting surgery. The expression of preproET-1 and of ECE-1a was upregulated ≈2- and 3-fold, respectively, in African Americans. In endothelium-intact vessels, the ET_A expression was higher in whites. In endothelium-denuded vessels, the ET_B mRNA was 3-fold higher in African Americans, suggesting that vasoconstriction-promoting ET_B receptors are upregulated in this population. Vascular tissue ET-1 levels and ECE-1 activity were also augmented in African. American patients. Conclusions - This study demonstrated that the biosynthetic pathway of ET-1 is activated to a higher degree and that the ET_B receptor subtype expression is altered in the peripheral vasculature of African American hypertensive patients. The augmented synthesis and altered expression of ET_B receptors may both contribute to the increased incidence of hypertension and related complications in this patient population.