Endothelin and vein bypass grafts in experimental atherosclerosis

Endothelin-1 (ET-1) is a potent vasoconstrictor whose serum concentration increases with the development of atherosclerosis. Coronary artery-vein bypass grafts are susceptible to vasospasm and to the development of accelerated atherosclerosis. Although ET-1 is thought to play a role in coronary vasospasm, the effect of ET-1 in atherosclerotic vein grafts is unknown. The responses of veins, arteries, and vein bypass grafts from normolipidemic and hyperlipidemic animals to ET-1 were therefore investigated. Vein bypass grafts were placed in the carotid position of 12 New Zealand White rabbits. Seven were fed a 1% cholesterol diet for 4 weeks before surgery and thereafter until harvest (hyperlipidemia), and five were fed a normal diet (normolipidemia). Vein grafts, contralateral common carotid arteries, and jugular veins were harvested 4 weeks after surgery. Whereas there were no histologic changes in veins or carotids, normolipidemic vein grafts developed intimal hyperplasia and hyperlipidemic vein grafts developed atherosclerosis. Isometric tension studies with ET-1 (10(-12) to 10(-6) M) showed that hyperlipidemia increased the maximal tension generated to ET-1 in the veins (660 +/- 80 to 1,110 +/- 140 mg, mean +/- SEM; p < 0.05), carotids (150 +/- 30 mg to 540 +/- 120 mg; p < 0.05), and vein grafts (180 +/- 20 to 450 +/- 60 mg; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)