title: Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia.
abstract: Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic (n = 14) and nonischemic (n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean internal diameter 313 +/- 11 micrometers) were mounted on a wire myograph for measurement of morphology and isometric tension. Vasodilation was examined after preconstriction with U-46619, a thromboxane A2 analog. Endothelium-dependent relaxation to acetylcholine and bradykinin was impaired in patients with ischemic compared with nonischemic cardiomyopathy (P < 0.01 and P < 0.001, respectively). Endothelium-independent relaxation to sodium nitroprusside was preserved. Incubation with L-arginine (3 mmol/l) did not improve endothelium-dependent relaxation to acetylcholine or bradykinin. With the use of stepwise multivariate analysis, hypercholesterolemia, but no other risk factor for atherosclerosis, was independently associated with impaired endothelium-dependent relaxation to acetylcholine (r = -0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobstructive epicardial atherosclerosis and hypercholesterolemia to myocardial ischemia.
authors.affiliation: Department of Medicine, University Hospital of South Manchester, Manchester M23 9LT, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Cooper
authors.forename: A M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D009202:Cardiomyopathies / Q000503:physiopathology / Q000601:surgery; D003326:Coronary Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D006937:Hypercholesterolemia / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D009599:Nitroprusside; D013373:Substance P; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D001920:Bradykinin