Endothelium-dependent relaxation to aggregating platelets in isolated basilar arteries of control and hypercholesterolemic pigs

Circ Res. 1988 Sep;63(3):604-12. doi: 10.1161/01.res.63.3.604.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basilar Artery / physiology
  • Basilar Artery / physiopathology*
  • Blood Platelets / physiology*
  • Endothelium, Vascular / physiology
  • Endothelium, Vascular / physiopathology*
  • Hypercholesterolemia / physiopathology*
  • In Vitro Techniques
  • Male
  • Platelet Aggregation*
  • Reference Values
  • Swine
  • Vasoconstriction
  • Vasodilation*