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. 1986 Aug;78(2):539–544. doi: 10.1172/JCI112606

Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries. Role of serotonin, thromboxane A2, and adenine nucleotides.

D S Houston, J T Shepherd, P M Vanhoutte
PMCID: PMC423591  PMID: 3734103

Abstract

Aggregating human platelets contract isolated rings of canine coronary artery without endothelium, but relax rings with intact endothelium. We performed experiments to identify the substances released from platelets responsible for these effects. The contraction in rings without endothelium was reduced by treating the platelets with thromboxane synthetase inhibitor, dazoxiben, or treating the vessels with the thromboxane-receptor antagonist, SQ 29548. The serotonergic antagonist, methiothepin, also reduced the platelet-induced contraction. The combination of methiothepin plus dazoxiben or SQ 29548 caused a further inhibition. The endothelium-dependent relaxation to platelets during contractions evoked by prostaglandin F2 alpha was nearly abolished by the ADP- and ATP-scavenger, apyrase. It was not inhibited by methiothepin, which antagonizes endothelium-dependent relaxations to serotonin. Thus, both serotonin and thromboxane A2 contribute to the direct activation of coronary smooth muscle by aggregating human platelets, whereas adenine nucleotides are the principal mediators of the endothelium-dependent relaxation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bing R. J., Burger W., Chemnitius J. M., Saeed M., Metz M. Z. Effect of intact endothelium against platelet-induced coronary artery spasm in isolated rabbit hearts. Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1596–1600. doi: 10.1016/0002-9149(85)90979-8. [DOI] [PubMed] [Google Scholar]
  2. Brazenor R. M., Angus J. A. Actions of serotonin antagonists on dog coronary artery. Eur J Pharmacol. 1982 Jul 30;81(4):569–576. doi: 10.1016/0014-2999(82)90346-6. [DOI] [PubMed] [Google Scholar]
  3. Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
  4. Cohen R. A., Shepherd J. T., Vanhoutte P. M. 5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries. Am J Physiol. 1983 Dec;245(6):H1077–H1080. doi: 10.1152/ajpheart.1983.245.6.H1077. [DOI] [PubMed] [Google Scholar]
  5. Cohen R. A., Shepherd J. T., Vanhoutte P. M. Endothelium and asymmetrical responses of the coronary arterial wall. Am J Physiol. 1984 Sep;247(3 Pt 2):H403–H408. doi: 10.1152/ajpheart.1984.247.3.H403. [DOI] [PubMed] [Google Scholar]
  6. Cohen R. A., Shepherd J. T., Vanhoutte P. M. Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets. Science. 1983 Jul 15;221(4607):273–274. doi: 10.1126/science.6574604. [DOI] [PubMed] [Google Scholar]
  7. De Mey J. G., Claeys M., Vanhoutte P. M. Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery. J Pharmacol Exp Ther. 1982 Jul;222(1):166–173. [PubMed] [Google Scholar]
  8. De Mey J. G., Vanhoutte P. M. Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol. 1981 Jul;316:347–355. doi: 10.1113/jphysiol.1981.sp013792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ellis E. F., Oelz O., Roberts L. J., 2nd, Payne N. A., Sweetman B. J., Nies A. S., Oates J. A. Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2. Science. 1976 Sep 17;193(4258):1135–1137. doi: 10.1126/science.959827. [DOI] [PubMed] [Google Scholar]
  10. Engel G., Göthert M., Müller-Schweinitzer E., Schlicker E., Sistonen L., Stadler P. A. Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(2):116–124. doi: 10.1007/BF00497016. [DOI] [PubMed] [Google Scholar]
  11. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  12. Hammond D. L., Tyce G. M., Yaksh T. L. Efflux of 5-hydroxytryptamine and noradrenaline into spinal cord superfusates during stimulation of the rat medulla. J Physiol. 1985 Feb;359:151–162. doi: 10.1113/jphysiol.1985.sp015579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Houston D. S., Gerrard J. M., McCrea J., Glover S., Butler A. M. The influence of amines on various platelet responses. Biochim Biophys Acta. 1983 Oct 12;734(2):267–273. doi: 10.1016/0005-2736(83)90124-4. [DOI] [PubMed] [Google Scholar]
  14. Houston D. S., Shepherd J. T., Vanhoutte P. M. Adenine nucleotides, serotonin, and endothelium-dependent relaxations to platelets. Am J Physiol. 1985 Mar;248(3 Pt 2):H389–H395. doi: 10.1152/ajpheart.1985.248.3.H389. [DOI] [PubMed] [Google Scholar]
  15. Lamping K. G., Marcus M. L., Dole W. P. Removal of the endothelium potentiates canine large coronary artery constrictor responses to 5-hydroxytryptamine in vivo. Circ Res. 1985 Jul;57(1):46–54. doi: 10.1161/01.res.57.1.46. [DOI] [PubMed] [Google Scholar]
  16. McGrath M. A. 5-hydroxytryptamine and neurotransmitter release in canine blood vessels. Inhibition by low and augmentation by high concentrations. Circ Res. 1977 Oct;41(4):428–435. doi: 10.1161/01.res.41.4.428. [DOI] [PubMed] [Google Scholar]
  17. Meyers K. M., Holmsen H., Seachord C. L. Comparative study of platelet dense granule constituents. Am J Physiol. 1982 Sep;243(3):R454–R461. doi: 10.1152/ajpregu.1982.243.3.R454. [DOI] [PubMed] [Google Scholar]
  18. Moulds R. F., Iwanov V., Medcalf R. L. The effects of platelet-derived contractile agents on human digital arteries. Clin Sci (Lond) 1984 Apr;66(4):443–451. doi: 10.1042/cs0660443. [DOI] [PubMed] [Google Scholar]
  19. Mullane K. M., Bradley G., Moncada S. The interactions of platelet-derived mediators on isolated canine coronary arteries. Eur J Pharmacol. 1982 Oct 15;84(1-2):115–118. doi: 10.1016/0014-2999(82)90166-2. [DOI] [PubMed] [Google Scholar]
  20. Ogletree M. L., Harris D. N., Greenberg R., Haslanger M. F., Nakane M. Pharmacological actions of SQ 29,548, a novel selective thromboxane antagonist. J Pharmacol Exp Ther. 1985 Aug;234(2):435–441. [PubMed] [Google Scholar]
  21. Powell W. S. Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica. Prostaglandins. 1980 Nov;20(5):947–957. doi: 10.1016/0090-6980(80)90144-6. [DOI] [PubMed] [Google Scholar]
  22. Randall M. J., Parry M. J., Hawkeswood E., Cross P. E., Dickinson R. P. UK-37, 248, a novel, selective thromboxane synthetase inhibitor with platelet anti-aggregatory and anti-thrombotic activity. Thromb Res. 1981 Jul 1;23(1-2):145–162. doi: 10.1016/0049-3848(81)90247-4. [DOI] [PubMed] [Google Scholar]
  23. Reibel D. K., Roth D. M., Lefer B. L., Lefer A. M. Hyperreactivity of coronary vasculature in platelet-perfused hearts from diabetic rats. Am J Physiol. 1983 Oct;245(4):H640–H645. doi: 10.1152/ajpheart.1983.245.4.H640. [DOI] [PubMed] [Google Scholar]
  24. Rubanyi G. M., Lorenz R. R., Vanhoutte P. M. Bioassay of endothelium-derived relaxing factor(s): inactivation by catecholamines. Am J Physiol. 1985 Jul;249(1 Pt 2):H95–101. doi: 10.1152/ajpheart.1985.249.1.H95. [DOI] [PubMed] [Google Scholar]
  25. Van Nueten J. M., Janssen P. A., Van Beek J., Xhonneux R., Verbeuren T. J., Vanhoutte P. M. Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther. 1981 Jul;218(1):217–230. [PubMed] [Google Scholar]
  26. Van Nueten J. M., Leysen J. E., de Clerck F., Vanhoutte P. M. Serotonergic receptor subtypes and vascular reactivity. J Cardiovasc Pharmacol. 1984;6 (Suppl 4):S564–S574. doi: 10.1097/00005344-198406004-00003. [DOI] [PubMed] [Google Scholar]
  27. Vanhoutte P. M., Houston D. S. Platelets, endothelium, and vasospasm. Circulation. 1985 Oct;72(4):728–734. doi: 10.1161/01.cir.72.4.728. [DOI] [PubMed] [Google Scholar]

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