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)
Davies
M G
MG
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Klyachkin
M L
ML
Kim
J H
JH
Hagen
P O
PO
D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000503:physiopathology*; D004036:Diet, Atherogenic; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D006949:Hyperlipidemias / Q000097:blood / Q000503:physiopathology; D007537:Isometric Contraction / Q000502:physiology; D007601:Jugular Veins / Q000187:drug effects / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011817:Rabbits; D014182:Transplantation, Autologous
D016232:Endothelins; D002784:Cholesterol