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. 1993 Sep;110(1):360–368. doi: 10.1111/j.1476-5381.1993.tb13818.x

Comparison of contractile responses to 5-hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A2-receptor agonist, U46619.

T M Cocks 1, B K Kemp 1, D Pruneau 1, J A Angus 1
PMCID: PMC2176043  PMID: 8220898

Abstract

1. The interaction between the thromboxane A2 receptor agonist, U46619 and two 5-hydroxytryptamine (5-HT) receptor agonists, the non-selective, naturally occurring agonist, 5-HT and the selective 5-HT1-like agonist, sumatriptan were studied in human epicardial coronary arteries in vitro. 2. Coronary artery rings (2-4 mm in diameter) were prepared from epicardial arteries from explant hearts of patients undergoing heart transplant (cardiomyopathy, n = 13; ischaemic heart disease, n = 10) and unused donor hearts (n = 5). Each ring of artery was set at optimal resting conditions to record changes in isometric force. 3. The majority of artery rings developed phasic, rhythmic contractions either spontaneously or in response to all vasoconstrictor agonists tested. Both the spontaneous and agonist-induced phasic contractions were abolished by nifedipine (0.1 microM). 4. Concentration-contraction curves to 5-HT-receptor agonists and noradrenaline (NA), were first constructed in artery rings that did not develop phasic activity. 5-HT and ergometrine were the most potent agonists with EC50 values of 6.8 +/- 0.2 and 7.7 +/- 0.2 (-log M) respectively. Potencies (EC50's) to sumatriptan, methysergide and noradrenaline could not be determined due to their poor ability to contract the coronary artery. Maximum contractions (Emax; normalized as a percentage of the contraction to a maximum-depolarizing concentration of K+ in physiological salt solution (KPSS)) for 5-HT, ergometrine, sumatriptan, methysergide and noradrenaline were 40 +/- 10, 9 +/- 3, < 5, < 5 and < 5% respectively. 5. In arteries without phasic activity, U46619 (1 nM) caused an increase in force of 3.8 +/- 1% KPSS.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Angus J. A. 5-HT receptors in the coronary circulation. Trends Pharmacol Sci. 1989 Mar;10(3):89–90. doi: 10.1016/0165-6147(89)90197-1. [DOI] [PubMed] [Google Scholar]
  2. Angus J. A., Brazenor R. M. Relaxation of large coronary artery by verapamil, D600, and nifedipine is constrictor selective: comparison with glyceryl trinitrate. J Cardiovasc Pharmacol. 1983 Mar-Apr;5(2):321–328. doi: 10.1097/00005344-198303000-00026. [DOI] [PubMed] [Google Scholar]
  3. Angus J. A., Cocks T. M., Satoh K. Alpha 2-adrenoceptors and endothelium-dependent relaxation in canine large arteries. Br J Pharmacol. 1986 Aug;88(4):767–777. doi: 10.1111/j.1476-5381.1986.tb16249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ashton J. H., Ogletree M. L., Michel I. M., Golino P., McNatt J. M., Taylor A. L., Raheja S., Schmitz J., Buja L. M., Campbell W. B. Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses. Circulation. 1987 Oct;76(4):952–959. doi: 10.1161/01.cir.76.4.952. [DOI] [PubMed] [Google Scholar]
  5. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  6. Brazenor R. M., Angus J. A. Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: no role for alpha adrenoceptors. J Pharmacol Exp Ther. 1981 Aug;218(2):530–536. [PubMed] [Google Scholar]
  7. Castle W. M., Simmons V. E. Coronary vasospasm and sumatriptan. BMJ. 1992 Jul 11;305(6845):117–118. doi: 10.1136/bmj.305.6845.117-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chester A. H., Martin G. R., Bodelsson M., Arneklo-Nobin B., Tadjkarimi S., Tornebrandt K., Yacoub M. H. 5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res. 1990 Nov;24(11):932–937. doi: 10.1093/cvr/24.11.932. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Connor H. E., Feniuk W., Humphrey P. P. 5-Hydroxytryptamine contracts human coronary arteries predominantly via 5-HT2 receptor activation. Eur J Pharmacol. 1989 Feb 14;161(1):91–94. doi: 10.1016/0014-2999(89)90184-2. [DOI] [PubMed] [Google Scholar]
  12. Connor H. E., Feniuk W., Humphrey P. P. Characterization of 5-HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5-HT1-like receptor agonist. Br J Pharmacol. 1989 Feb;96(2):379–387. doi: 10.1111/j.1476-5381.1989.tb11828.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Curtin T., Brooks A. P., Roberts J. A. Cardiorespiratory distress after sumatriptan given by injection. BMJ. 1992 Sep 19;305(6855):713–714. doi: 10.1136/bmj.305.6855.713-d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. De Caterina R., Carpeggiani C., L'Abbate A. A double-blind, placebo-controlled study of ketanserin in patients with Prinzmetal's angina. Evidence against a role for serotonin in the genesis of coronary vasospasm. Circulation. 1984 May;69(5):889–894. doi: 10.1161/01.cir.69.5.889. [DOI] [PubMed] [Google Scholar]
  15. Egashira K., Tomoike H., Hayashi Y., Yamada A., Nakamura M., Takeshita A. Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury. Circ Res. 1992 Aug;71(2):435–442. doi: 10.1161/01.res.71.2.435. [DOI] [PubMed] [Google Scholar]
  16. Elghozi J. L., Head G. A. Spinal noradrenergic pathways and pressor responses to central angiotensin II. Am J Physiol. 1990 Jan;258(1 Pt 2):H240–H246. doi: 10.1152/ajpheart.1990.258.1.H240. [DOI] [PubMed] [Google Scholar]
  17. Feniuk W., Humphrey P. P., Perren M. J. GR43175 does not share the complex pharmacology of the ergots. Cephalalgia. 1989;9 (Suppl 9):35–39. doi: 10.1111/J.1468-2982.1989.TB00070.X. [DOI] [PubMed] [Google Scholar]
  18. Feniuk W., Humphrey P. P., Perren M. J. The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs. Br J Pharmacol. 1989 Jan;96(1):83–90. doi: 10.1111/j.1476-5381.1989.tb11787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Freedman S. B., Chierchia S., Rodriguez-Plaza L., Bugiardini R., Smith G., Maseri A. Ergonovine-induced myocardial ischemia: no role for serotonergic receptors? Circulation. 1984 Aug;70(2):178–183. doi: 10.1161/01.cir.70.2.178. [DOI] [PubMed] [Google Scholar]
  20. Golino P., Ashton J. H., Buja L. M., Rosolowsky M., Taylor A. L., McNatt J., Campbell W. B., Willerson J. T. Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and serotonin are possible mediators. Circulation. 1989 Jan;79(1):154–166. doi: 10.1161/01.cir.79.1.154. [DOI] [PubMed] [Google Scholar]
  21. Golino P., Piscione F., Willerson J. T., Cappelli-Bigazzi M., Focaccio A., Villari B., Indolfi C., Russolillo E., Condorelli M., Chiariello M. Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med. 1991 Mar 7;324(10):641–648. doi: 10.1056/NEJM199103073241001. [DOI] [PubMed] [Google Scholar]
  22. Holtz J., Held W., Sommer O., Kühne G., Bassenge E. Ergonovine-induced constrictions of epicardial coronary arteries in conscious dogs: alpha-adrenoceptors are not involved. Basic Res Cardiol. 1982 May-Jun;77(3):278–291. doi: 10.1007/BF01908043. [DOI] [PubMed] [Google Scholar]
  23. Humphrey P. P., Feniuk W. Mode of action of the anti-migraine drug sumatriptan. Trends Pharmacol Sci. 1991 Dec;12(12):444–446. doi: 10.1016/0165-6147(91)90630-b. [DOI] [PubMed] [Google Scholar]
  24. Humphrey P. P., Feniuk W., Perren M. J., Connor H. E., Oxford A. W., Coates L. H., Butina D. GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol. 1988 Aug;94(4):1123–1132. doi: 10.1111/j.1476-5381.1988.tb11630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kalsner S. Coronary artery reactivity in human vessels: some questions and some answers. Fed Proc. 1985 Feb;44(2):321–325. [PubMed] [Google Scholar]
  26. Kawachi Y., Tomoike H., Maruoka Y., Kikuchi Y., Araki H., Ishii Y., Tanaka K., Nakamura M. Selective hypercontraction caused by ergonovine in the canine coronary artery under conditions of induced atherosclerosis. Circulation. 1984 Feb;69(2):441–450. doi: 10.1161/01.cir.69.2.441. [DOI] [PubMed] [Google Scholar]
  27. Kimura T., Yasue H., Sakaino N., Rokutanda M., Jougasaki M., Araki H. Effects of magnesium on the tone of isolated human coronary arteries. Comparison with diltiazem and nitroglycerin. Circulation. 1989 May;79(5):1118–1124. doi: 10.1161/01.cir.79.5.1118. [DOI] [PubMed] [Google Scholar]
  28. MacLennan S. J., Martin G. R. Actions of non-peptide ergot alkaloids at 5-HT1-like and 5-HT2 receptors mediating vascular smooth muscle contraction. Naunyn Schmiedebergs Arch Pharmacol. 1990 Aug;342(2):120–129. doi: 10.1007/BF00166953. [DOI] [PubMed] [Google Scholar]
  29. Macintyre P. D., Bhargava B., Hogg K. J., Gemmill J. D., Hillis W. S. The effect of i.v. sumatriptan, a selective 5-HT1-receptor agonist on central haemodynamics and the coronary circulation. Br J Clin Pharmacol. 1992 Dec;34(6):541–546. [PMC free article] [PubMed] [Google Scholar]
  30. Martin W., Furchgott R. F., Villani G. M., Jothianandan D. Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther. 1986 May;237(2):529–538. [PubMed] [Google Scholar]
  31. McFadden E. P., Bauters C., Lablanche J. M., Leroy F., Clarke J. G., Henry M., Schandrin C., Davies G. J., Maseri A., Bertrand M. E. Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients. Circulation. 1992 Jul;86(1):187–195. doi: 10.1161/01.cir.86.1.187. [DOI] [PubMed] [Google Scholar]
  32. McFadden E. P., Clarke J. G., Davies G. J., Kaski J. C., Haider A. W., Maseri A. Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina. N Engl J Med. 1991 Mar 7;324(10):648–654. doi: 10.1056/NEJM199103073241002. [DOI] [PubMed] [Google Scholar]
  33. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  34. Moskowitz M. A. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci. 1992 Aug;13(8):307–311. doi: 10.1016/0165-6147(92)90097-p. [DOI] [PubMed] [Google Scholar]
  35. Mulvany M. J., Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977 Jul;41(1):19–26. doi: 10.1161/01.res.41.1.19. [DOI] [PubMed] [Google Scholar]
  36. Müller-Schweinitzer E. The mechanism of ergometrine-induced coronary arterial spasm: in vitro studies on canine arteries. J Cardiovasc Pharmacol. 1980 Sep-Oct;2(5):645–655. doi: 10.1097/00005344-198009000-00013. [DOI] [PubMed] [Google Scholar]
  37. Nielsen T. H., Tfelt-Hansen P. Lack of effect of GR43175 on peripheral arteries in man. Cephalalgia. 1989;9 (Suppl 9):93–95. doi: 10.1111/J.1468-2982.1989.TB00080.X. [DOI] [PubMed] [Google Scholar]
  39. Parsons A. A., Whalley E. T., Feniuk W., Connor H. E., Humphrey P. P. 5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of human isolated basilar artery. Br J Pharmacol. 1989 Feb;96(2):434–440. doi: 10.1111/j.1476-5381.1989.tb11835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Perren M. J., Feniuk W., Humphrey P. P. The selective closure of feline carotid arteriovenous anastomoses (AVAs) by GR43175. Cephalalgia. 1989;9 (Suppl 9):41–46. doi: 10.1111/J.1468-2982.1989.TB00071.X. [DOI] [PubMed] [Google Scholar]
  41. Perrin V. L., Färkkilä M., Goasguen J., Doenicke A., Brand J., Tfelt-Hansen P. Overview of initial clinical studies with intravenous and oral GR43175 in acute migraine. Cephalalgia. 1989;9 (Suppl 9):63–72. doi: 10.1111/J.1468-2982.1989.TB00075.X. [DOI] [PubMed] [Google Scholar]
  42. Quillen J. E., Sellke F. W., Armstrong M. L., Harrison D. G. Long-term cholesterol feeding alters the reactivity of primate coronary microvessels to platelet products. Arterioscler Thromb. 1991 May-Jun;11(3):639–644. doi: 10.1161/01.atv.11.3.639. [DOI] [PubMed] [Google Scholar]
  43. Ross G., Stinson E., Schroeder J., Ginsburg R. Spontaneous phasic activity of isolated human coronary arteries. Cardiovasc Res. 1980 Oct;14(10):613–618. doi: 10.1093/cvr/14.10.613. [DOI] [PubMed] [Google Scholar]
  44. Sahin-Erdemli I., Hoyer D., Stoll A., Seiler M. P., Schoeffter P. 5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of guinea-pig isolated iliac artery. Br J Pharmacol. 1991 Feb;102(2):386–390. doi: 10.1111/j.1476-5381.1991.tb12183.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sakanashi M., Yonemura K. I. On the mode of action of ergometrine in the isolated dog coronary artery. Eur J Pharmacol. 1980 Jun 13;64(2-3):157–160. doi: 10.1016/0014-2999(80)90038-2. [DOI] [PubMed] [Google Scholar]
  46. Saxena P. R. Selective vasoconstriction in carotid vascular bed by methysergide: possible relevance to its antimigraine effect. Eur J Pharmacol. 1974 Jun;27(1):99–105. doi: 10.1016/0014-2999(74)90206-4. [DOI] [PubMed] [Google Scholar]
  47. Sumner M. J., Feniuk W., McCormick J. D., Humphrey P. P. Studies on the mechanism of 5-HT1 receptor-induced smooth muscle contraction in dog saphenous vein. Br J Pharmacol. 1992 Mar;105(3):603–608. doi: 10.1111/j.1476-5381.1992.tb09026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Takayanagi R., Ohnaka K., Takasaki C., Ohashi M., Nawata H. Multiple subtypes of endothelin receptors in human and porcine tissues: characterization by ligand binding, affinity labeling, and regional distribution. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S127–S130. doi: 10.1097/00005344-199100177-00034. [DOI] [PubMed] [Google Scholar]
  49. Toda N., Okamura T. Comparison of the response to 5-carboxamidotryptamine and serotonin in isolated human, monkey and dog coronary arteries. J Pharmacol Exp Ther. 1990 May;253(2):676–682. [PubMed] [Google Scholar]
  50. Treatment of migraine attacks with sumatriptan. The Subcutaneous Sumatriptan International Study Group. N Engl J Med. 1991 Aug 1;325(5):316–321. doi: 10.1056/NEJM199108013250504. [DOI] [PubMed] [Google Scholar]
  51. Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
  52. Willett F., Curzen N., Adams J., Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ. 1992 May 30;304(6839):1415–1415. doi: 10.1136/bmj.304.6839.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  54. Yang Z. H., Richard V., von Segesser L., Bauer E., Stulz P., Turina M., Lüscher T. F. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation. 1990 Jul;82(1):188–195. doi: 10.1161/01.cir.82.1.188. [DOI] [PubMed] [Google Scholar]
  55. Young M. S., Iwanov V., Moulds R. F. Interaction between platelet-released serotonin and thromboxane A2 on human digital arteries. Clin Exp Pharmacol Physiol. 1986 Feb;13(2):143–152. doi: 10.1111/j.1440-1681.1986.tb00328.x. [DOI] [PubMed] [Google Scholar]
  56. Zeiher A. M., Drexler H., Wollschläger H., Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation. 1991 Feb;83(2):391–401. doi: 10.1161/01.cir.83.2.391. [DOI] [PubMed] [Google Scholar]
  57. Zeiher A. M., Schächinger V., Weitzel S. H., Wollschläger H., Just H. Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Circulation. 1991 May;83(5):1519–1525. doi: 10.1161/01.cir.83.5.1519. [DOI] [PubMed] [Google Scholar]
  58. van Heuven-Nolsen D. 5-HT receptor subtype-specific drugs and the cardiovascular system. Trends Pharmacol Sci. 1988 Dec;9(12):423–425. doi: 10.1016/0165-6147(88)90123-x. [DOI] [PubMed] [Google Scholar]

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