ABSTRACT
The distribution of endothelin-1 (ET-1) receptors on human vascular tissue has been studied. High- and low-resolution autoradiography was used to determine the distribution of [125]ET binding sites in human blood vessels and ventricular myocardium. Dense, displaceable [125I]ET binding was associated with cardiac myocytes and the smooth muscle layer of all vessels were examined. There was also dense binding to vasa vasora. There was increased [125I]ET binding to atheromatous coronary arteries and vein graft, which was associated with the tunica media and vasa vasora or regions of neovascularization. Vasoconstrictor and positive inotropic activity of ET-1 has been established in vitro. The vasoconstrictor effect of ET-1 is likely to be mediated via the binding sites identified on vascular smooth muscle. The striking perivascular [125I]ET-1 binding suggests that ET-1 may also have constrictor activity on vasa vasora. There is experimental evidence that ET-1 has mitogenic activity on vascular smooth muscle cells in culture. The increased binding to both smooth muscle and regions of neovascularization in atheromatous vessels suggests that ET-1 may play a role in atherosclerosis.
Subject(s)
Blood Vessels/metabolism , Coronary Vessels/metabolism , Endothelins/metabolism , Adolescent , Adult , Aged , Arteriosclerosis/metabolism , Autoradiography , Binding Sites , Child , Child, Preschool , Female , Humans , Infant , Iodine Radioisotopes , Male , Middle Aged , Myocardium/metabolism , Receptors, Cell Surface/metabolism , Receptors, EndothelinABSTRACT
In vitro receptor autoradiography has been used to study the distribution of [(125)I]endothelin binding sites in human coronary tissue from patients undergoing cardiac transplantation. Dense binding of [(125)I]endothelin was associated with the smooth muscle of epicardial coronary arteries as well as to perivascular regions of these vessels. Binding was also associated with the ventricular myocardium. There was an increased binding of [(125)I]endothelin to atheromatous tissue, both coronary arteries and vein graft. The [(125)I]endothelin binding sites identified using in vitro autoradiography are likely to be functionally relevant since endothelin causes a concentration-dependent contraction of segments of human epicardial coronary arteries in vitro and also has positive inotropic activity on isolated human cardiomyocytes. The presence of specific binding sites for [(125)I]endothelin on coronary tissue and the increased binding in atheromatous tissue suggest that endothelin is a peptide which may play a role in the maintenance of vascular tone and/or the pathogenesis of ischaemic heart disease.
