Detection of Endothelin Receptors in Human Coronary Artery Vascular Smooth Muscle Cells But Not Endothelial Cells by Using Electron Microscope Autoradiography

Endothelin A (ETA) and ETB receptors located on vascular smooth-muscle cells mediate potent vasoconstriction in animal and human blood vessels. Although vascular endothelial ETB receptors mediate vasodilatation through release of nitric oxide, prostacyclin, or an endothelium-derived hyperpolarizing factor in animal vessels, there is less evidence to support ET-mediated endothelium-dependent relaxation in human arteries. We investigated the regional and subcellular localization of ET-receptor subtypes in human epicardial coronary arteries obtained from patients with congestive heart failure undergoing cardiac transplantation. Radioligand-binding studies revealed a predominance of the ETA-receptor subtype in the coronary artery. ETA and ETB receptors were located in the media and in perivascular structures by using macroautoradiography. Specific binding in the intimal layer was low. Autoradiography at the ultrastructural level revealed the presence of ETA and ETB receptors on medial vascular smooth-muscle cell plasmalemma and plasmalemmal vesicles with a predominance of the ETA subtype. ET receptors were not detected in either luminal endothelial cells of the coronary arteries or endothelial cells lining small adventitial blood vessels. This study is the first to identify the subcellular localization of ET receptors in human coronary artery vascular smooth-muscle cells. These receptors probably mediate the well-established vasoconstrictor response to ET-1. The inability to detect ET receptors on endothelial cells suggests a minor role for endothelial cells in ET-mediated vasodilatation of the coronary vasculature.