Distribution of endothelin-1 (ET) receptors (ETA and ETB) and immunoreactive ET-1 in porcine saphenous vein–carotid artery interposition grafts Original Research Article

Proliferation of vascular smooth muscle cells (VSMC) is a principal event in neointima formation in saphenous vein–coronary artery bypass grafts. Since endothelin-1 (ET-1) promotes VSMC replication and ET-1 receptor antagonists inhibit neointima formation in arterial injury models, it is reasonable to propose that ET-1 may be involved in neointima formation in vein grafts. However, it is not known what alterations of ET-1 and its receptors (if any) occur in vein grafts. The objective of this study, therefore, was to investigate the distribution of ET-1 and ET-1 receptor subtypes (ETA and ETB) in porcine vein grafts. Unilateral interposition saphenous vein grafting was performed by end to end anastomosis after excision of a segment of carotid artery in Landrace pigs. One month after surgery, vein grafts, ungrafted saphenous veins and carotid arteries were excised, ET-1 immunoreactivity identified by immunocytochemistry and ETA and ETB receptor subtypes studied using autoradiography. In vein grafts, there was a greater density of ETA compared to ETB receptors in both the tunica media and neointima. ETA binding in the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ET-1 binding (to both ETA and ETB receptors) was also associated with microvessels in the adventitia within the graft. In vein grafts, there was strong ETB binding to neutrophils which were present in high numbers at the subendothelium and within the adventitia. It is concluded ETA receptors may play a role in vein graft thickening at the medial and neointimal VSMC level, whereas ETB receptors may play a role in microangiogenesis. The higher levels of ETA receptors in the tunica media of ungrafted saphenous vein relative to the carotid artery and vein graft may also render this conduit susceptible to neointima formation. These data indicate that studies on the effect of ET receptor antagonists on the pathobiology of vein graft disease is warranted.