Constitutive nitric oxide synthase is expressed and nitric oxide-mediated relaxation is preserved in retrieved human aortocoronary vein grafts.
Although little is known about the endothelial cell function of human saphenous vein coronary artery bypass grafts, there is evidence to suggest that receptor-activated, endothelial-dependent relaxation mediated by nitric oxide is impaired. This study examines the expression and function of endothelial cell constitutive nitric oxide synthase (cNOS) of aortocoronary vein bypass grafts and human saphenous veins obtained from 10 patients undergoing repeat coronary artery bypass grafting for recurrent ischemic symptoms. Following precontraction with norepinephrine (10(-5) M), responses to acetylcholine (receptor-mediated, endothelium-dependent), calcium ionophore (A23187; receptor-independent, endothelium-dependent), and sodium nitroprusside (endothelium-independent) were assessed. Following total RNA extraction using phenol/guanidinium isothiocyanate from specimens of human saphenous vein and vein graft, a quantitative RNase Protection Assay (RPA) was performed using a cRNA riboprobe corresponding to a fragment of the human endothelial cell cNOS gene. Histologically, the vein grafts showed both intimal hyperplasia development and focal atherosclerosis formation compared to the saphenous veins. Scanning electron microscopy of the saphenous veins and the vein grafts showed an intact endothelium. Precontracted vein grafts did not relax in response to acetylcholine; in contrast, the saphenous vein relaxed in a dose-dependent manner to reach a maximal relaxation of 19 +/- 4% precontracted tension. Saphenous veins and vein grafts relaxed in response to A23187 with maximal relaxation of 92 +/- 5 and 73 +/- 13%, respectively. Both vessels relaxed in a dose dependent manner to sodium nitroprusside. RPA normalized to beta-actin showed similar levels of expression of endothelial cell cNOS equivalent to 1 pg of sense RNA in both the saphenous vein and vein graft.(ABSTRACT TRUNCATED AT 250 WORDS)
Davies
M G
MG
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Berkowitz
D E
DE
Hagen
P O
PO
D000368:Aged; D000594:Amino Acid Oxidoreductases / Q000032:analysis*; D000001:Calcimycin / Q000494:pharmacology; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D012501:Saphenous Vein / Q000201:enzymology / Q000502:physiology / Q000637:transplantation*; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D000001:Calcimycin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases