DISTRIBUTION OF ENDOTHELIN RECEPTORS IN ATHEROSCLEROTIC HUMAN CORONARY-ARTERIES

It has been suggested that the potent vasoconstricter and proliferativ e agent endothelin (ET) may contribute to the development and effects of atherosclerosis. The aim of this study was to use autoradiography t o examine the distribution of ET receptors in human coronary artery wi th a range of pre-atherosclerotic and atherosclerotic lesions. ET-1 re ceptors in epicardial coronary artery sections were visualized accordi ng to the binding of [I-125]ET-1 (100 pM), the ET(A)-selective radioli gand [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 musc le of the media of all arteries studied and ET(A) receptors, defined b y [I-125]PD151242 binding, predominated. Intense [I-125]BQ3020 binding to ET(A) receptors was apparent on perivascular structures, such as a dventitial lymphatics. In contrast, ET receptors were absent in neoint imal smooth muscle. In regions of recanalized organized thrombus, micr oautoradiography revealed ET(A) receptors on the smooth muscle of new vessels. Discrete clusters of ET(B) receptors were detected in section s through the atherosclerotic arterial wall. A similar pattern of stai ning for von Willebrand factor was seen in adjacent sections. This sug gests that ET(B) receptors are present on endothelial cells of neovasc ularization, penetrating the diseased media.