Systemic hypertension augments, whereas insulin-dependent diabetes down-regulates, endothelin A receptor expression in the mammary artery in coronary artery disease patients

Abstract

Background: Endothelin (ET) A receptor antagonism causes decreased vasodilation in hypertensive coronary arteries and decreased effects on coronary artery compliance in diabetic patients. Methods: We investigate the mRNA expression of ET-1, ETA and ETB receptors, using real time RT-PCR, in biopsies from the internal mammary artery obtained from 49 patients, 18 diabetics and 34 hypertensives, all undergoing coronary artery bypass grafting. Results: Hypertensive patients had higher ET-1 mRNA expression (16438 [8417, 23917]), than normotensive patients (2974 [2283, 18055], p=0.008). Diabetic patients had significantly lower ETA receptor levels than non-diabetic patients (455 [167, 1496] vs. 1660 [700, 3190], respectively, p = 0.003). Conclusions: Multivariate analysis demonstrated that the presence of systemic hypertension was the only independent predictor of log ETA receptor expression and log ET-1 expression, while insulin-dependent diabetes was negatively correlated with ETA receptor expression. ETB receptor expression was not correlated with any predictor. Systemic hypertension is associated with increased ET-1 and ETA receptor mRNA expression, whereas insulin-dependent diabetes down-regulates ETA receptor mRNA expression in the internal mammary artery in patients with coronary artery disease undergoing bypass grafting