title: Alterations of vascular reactivity in atherosclerosis.
abstract: We have previously found that vascular relaxation to acetylcholine and thrombin is markedly impaired in vessels from monkeys with diet-induced atherosclerosis. In the present study, we found that both normal and atherosclerotic vessels relaxed completely to the calcium ionophore A23187, which stimulates release of the endothelium-derived relaxing factor by nonreceptor-mediated mechanisms. Atherosclerotic vessels, however, were less sensitive to this agent. The finding that responses to the calcium ionophore were impaired in atherosclerosis suggests that abnormal endothelium-dependent relaxation in atherosclerotic vessels is not related entirely to alterations of thrombin and muscarinic receptors but may also be due to abnormal endothelium-derived relaxing factor production or transfer from the endothelium to the underlying vascular smooth muscle. Neither normal nor atherosclerotic iliac arteries constricted in response to acetylcholine when studied in the nonpreconstricted state. Constriction to acetylcholine in these vessels was not unmasked by removal of the endothelium. Thus, the smooth muscle of iliac vessels from monkeys contains few functioning muscarinic receptors. Impaired relaxation of atherosclerotic vessels to acetylcholine is not due to enhanced muscarinic-mediated constriction or to production of an endothelium-derived constricting factor. In vivo studies were performed to determine if alpha-adrenergic coronary vascular constriction is enhanced in the presence of atherosclerosis. In anesthetized monkeys, myocardial oxygen consumption was increased by two mechanisms, aortic occlusion and phenylephrine infusion. During both aortic occlusion and phenylephrine infusion, decreases in coronary vascular resistance were similar in control and atherosclerotic monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
authors.forename: D G
authors.initials: DG
authors.lastname: Harrison
authors.forename: P C
authors.initials: PC
authors.lastname: Freiman
authors.forename: M L
authors.initials: ML
authors.lastname: Armstrong
authors.forename: M L
authors.initials: ML
authors.lastname: Marcus
authors.forename: D D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D001688:Biological Products / Q000378:metabolism; D001808:Blood Vessels / Q000503:physiopathology*; D000001:Calcimycin / Q000494:pharmacology; D002791:Cholesterol, Dietary; D003331:Coronary Vessels / Q000503:physiopathology; D004727:Endothelium / Q000503:physiopathology; D008252:Macaca fascicularis; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001688:Biological Products; D002791:Cholesterol, Dietary; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009569:Nitric Oxide; D000001:Calcimycin; D000109:Acetylcholine