DISTRIBUTION OF ENDOTHELIN RECEPTORS IN ATHEROSCLEROTIC HUMAN CORONARY-ARTERIES

It has been suggested that the potent vasoconstricter and proliferative agent endothelin (ET) may contribute to the development and effects of atherosclerosis. The aim of this study was to use autoradiography to examine the distribution of ET receptors in human coronary artery with a range of pre-atherosclerotic and atherosclerotic lesions. ET-1 receptors in epicardial coronary artery sections were visualized according to the binding of [I-125]ET-1 (100 pM), the ET(A)-selective radioligand [I-125]PD151242 (100 pM), and the ET(B)-selective [I-125]BQ3020 (300 pM). Dense [I-125]ET-1 binding was demonstrated in the smooth muscle of the media of all arteries studied and ET(A) receptors, defined by [I-125]PD151242 binding, predominated. Intense [I-125]BQ3020 binding to ET(A) receptors was apparent on perivascular structures, such as adventitial lymphatics. In contrast, ET receptors were absent in neointimal smooth muscle. In regions of recanalized organized thrombus, microautoradiography revealed ET(A) receptors on the smooth muscle of new vessels. Discrete clusters of ET(B) receptors were detected in sections through the atherosclerotic arterial wall. A similar pattern of staining for von Willebrand factor was seen in adjacent sections. This suggests that ET(B) receptors are present on endothelial cells of neovascularization, penetrating the diseased media.