title: Endothelium-dependent relaxation to aggregating platelets in isolated basilar arteries of control and hypercholesterolemic pigs.
abstract: The role of the endothelium was examined in the response to aggregating platelets in cerebral arteries from normal and hypercholesterolemic animals. Male Yorkshire pigs were fed either a normal diet or a 2% high-cholesterol diet for 10 weeks. Endothelium-dependent responses were examined in vitro. In rings of basilar arteries from control animals aggregating platelets caused endothelium-dependent relaxations, which were significantly inhibited by apyrase, an adenosine diphosphatase and triphosphatase, but were augmented by methiothepin, a combined S1- and S2-serotonergic blocker. In quiescent rings platelets induced contractions that were inhibited by the presence of the endothelium; these contractions were significantly inhibited by methiothepin, but not by ketanserin (an S2-serotonergic blocker) or dazoxiben (a thromboxane-synthetase blocker) in the presence or absence of SQ29548 (a thromboxane-receptor blocker). Adenosine diphosphate but not serotonin caused endothelium-dependent relaxations. In cholesterol-fed animals the endothelium-dependent relaxations in response to aggregating platelets and adenosine diphosphate were impaired. These experiments indicate that 1) the endothelium inhibits the vasoconstrictor effect of aggregating platelets in porcine cerebral arteries; 2) platelet-induced relaxations are achieved mainly by a purinergic mechanism, while platelet-induced contractions are mediated by activation of S1-serotonergic receptors with little contribution of thromboxanes; and 3) hypercholesterolemia impairs the endothelium-dependent relaxations in response to aggregating platelets due to the impaired responses to adenosine diphosphate.
authors.affiliation: Department of Physiology and Biophysics, Mayo Clinic, Rochester, MN 55905.
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: P
authors.initials: P
authors.lastname: Kim
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000502:physiology / Q000503:physiopathology*; D001792:Blood Platelets / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation; D012016:Reference Values; D013552:Swine; D014661:Vasoconstriction; D014664:Vasodilation