DISTRIBUTION OF ENDOTHELIN-1 (ET) RECEPTORS (ETA AND ETB) AND IMMUNOREACTIVE ET-1 IN PORCINE SAPHENOUS-VEIN CAROTID-ARTERY INTERPOSITION GRAFTS

Proliferation of vascular smooth muscle cells (VSMC) is a principal ev ent in neointima formation in saphenous vein-coronary artery bypass gr afts. Since endothelin-l (ET-1) promotes VSMC replication and ET-I rec eptor antagonists inhibit neointima formation in arterial injury model s, 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 o f this study, therefore, was to investigate the distribution of ET-I a nd ET-I receptor subtypes (ETA and ETB) in porcine vein grafts. Unilat eral 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 b y immunocytochemistry and ETA and ETB receptor subtypes studied using autoradiography. In vein grafts, there was a greater density of ETA co mpared to ETB receptors in both the tunica media and neointima. ETA bi nding in the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein gr aft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Den se ET-1 binding (10 both ETA and ETB receptors) was also associated wi th microvessels in the adventitia within the graft. In vein grafts, th ere was strong ETA binding to neutrophils which were present in high n umbers at the subendothelium and within the adventitia. It is conclude d 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 m icroangiogenesis. The higher levels of ETA receptors in the tunica med ia 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 antago nists on the pathobiology of vein graft disease is warranted. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.