Distribution of endothelin-1 (ET) receptors (ET(A) and ET(B)) and immunoreactive ET-1 in porcine saphenous vein-carotid artery interposition grafts.

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 (ET(A) and ET(B)) 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 ET(A) and ET(B) receptor subtypes studied using autoradiography. In vein grafts, there was a greater density of ET(A) compared to ET(B) receptors in both the tunica media and neointima. ET(A) 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 ET(A) and ET(B) receptors) was also associated with microvessels in the adventitia within the graft. In vein grafts, there was strong ET(B) binding to neutrophils which were present in high numbers at the subendothelium and within the adventitia. It is concluded ET(A) receptors may play a role in vein graft thickening at the medial and neointimal VSMC level, whereas ET(B) receptors may play a role in microangiogenesis. The higher levels of ET(A) 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.