Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Nov;34(5):409–414.

Effects of leukotrienes C4 and D4 on human isolated saphenous veins.

S P Allen 1, A H Chester 1, P J Piper 1, A P Sampson 1, E S Akl 1, M H Yacoub 1
PMCID: PMC1381469  PMID: 1467135

Abstract

1. Vascular injury during the intra-operative procedures of bypass surgery may be the initiating event in the gradual deterioration in the patency of the graft. Adhesion of leukocytes to the vascular endothelium frequently accompanies preparation and insertion of the graft. However, little is known about the effects of vasoactive substances released from leukocytes on vein graft performance. 2. To determine whether leukotrienes are capable of affecting the tone of blood vessels used as coronary artery bypass grafts we studied the human saphenous vein as intact rings using an isolated organ bath technique. 3. LTC4 and LTD4 caused weak endothelium-dependent relaxations at lower concentrations (1 pM to 1 nM) and powerful endothelium-independent contractions at higher concentrations (3 nM to 0.1 microM). The maximum responses to LTC4 and LTD4 for relaxations were 21.1 +/- 4.8% and 28.6 +/- 3.4% (% of noradrenaline induced tone) respectively and 64.6 +/- 9.9% and 59.1 +/- 7.9% (% response to KCl) respectively for contractions. 4. The inhibitor of nitric oxide formation, L-NG-monomethyl L-arginine, prevented the relaxations to LTD4, but not LTC4 and unmasked endothelium-dependent contractions to LTD4 (32.9 +/- 11.3%). NG-monomethyl L-arginine had no effect on the contractions produced by LTC4 or LTD4. 5. Indomethacin augmented relaxations and contractions of saphenous vein to LTC4 from 22.5 +/- 5.6 to 40.02 +/- 8.7 (P < 0.05) and 48.8 +/- 5.5% to 74.7 +/- 7.6% (P < 0.01) respectively. LTD4 responses were not affected by indomethacin treatment. 6. In conclusion, leukotrienes mediate biphasic responses in the human saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
409

Selected References

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

  1. Addonizio V. P., Wetstein L., Fisher C. A., Feldman P., Strauss J. F., 3rd, Harken A. H. Platelet-mediated cardiac ischemia. J Surg Res. 1982 Nov;33(5):402–408. doi: 10.1016/0022-4804(82)90055-5. [DOI] [PubMed] [Google Scholar]
  2. Ahmed T., Marchette B., Wanner A., Yerger L. Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations. Am Rev Respir Dis. 1985 Apr;131(4):554–558. doi: 10.1164/arrd.1985.131.4.554. [DOI] [PubMed] [Google Scholar]
  3. Angelini G. D., Bryan A. J., Williams H. M., Morgan R., Newby A. C. Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts. J Thorac Cardiovasc Surg. 1990 Mar;99(3):433–439. [PubMed] [Google Scholar]
  4. Baumann F. G., Catinella F. P., Cunningham J. N., Jr, Spencer F. C. Vein contraction and smooth muscle cell extensions as causes of endothelial damage during graft preparation. Ann Surg. 1981 Aug;194(2):199–211. doi: 10.1097/00000658-198108000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baumgartner H. R., Muggli R., Tschopp T. B., Turitto V. T. Platelet adhesion, release and aggregation in flowing blood: effects of surface properties and platelet function. Thromb Haemost. 1976 Feb 29;35(1):124–138. [PubMed] [Google Scholar]
  6. Berkowitz B. A., Zabko-Potapovich B., Valocik R., Gleason J. G. Effects of the leukotrienes on the vasculature and blood pressure of different species. J Pharmacol Exp Ther. 1984 Apr;229(1):105–112. [PubMed] [Google Scholar]
  7. Bonchek L. I. Prevention of endothelial damage during preparation of saphenous veins for bypass grafting. J Thorac Cardiovasc Surg. 1980 Jun;79(6):911–915. [PubMed] [Google Scholar]
  8. Carry M., Korley V., Willerson J. T., Weigelt L., Ford-Hutchinson A. W., Tagari P. Increased urinary leukotriene excretion in patients with cardiac ischemia. In vivo evidence for 5-lipoxygenase activation. Circulation. 1992 Jan;85(1):230–236. doi: 10.1161/01.cir.85.1.230. [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. Cramer E. B., Pologe L., Pawlowski N. A., Cohn Z. A., Scott W. A. Leukotriene C promotes prostacyclin synthesis by human endothelial cells. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4109–4113. doi: 10.1073/pnas.80.13.4109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dreyfuss F., Zahavi J. Adenosine diphosphate induced platelet aggregation in myocardial infarction and ischemic heart disease. Atherosclerosis. 1973 Jan-Feb;17(1):107–120. doi: 10.1016/0021-9150(73)90139-1. [DOI] [PubMed] [Google Scholar]
  13. Feuerstein G., Zukowska-Grojec Z., Kopin I. J. Cardiovascular effects of leukotriene D4 in SHR and WKY rats. Eur J Pharmacol. 1981 Nov 19;76(1):107–110. doi: 10.1016/0014-2999(81)90017-0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fuster V., Chesebro J. H. Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease. Circulation. 1986 Feb;73(2):227–232. doi: 10.1161/01.cir.73.2.227. [DOI] [PubMed] [Google Scholar]
  16. Hirsh P. D., Hillis L. D., Campbell W. B., Firth B. G., Willerson J. T. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med. 1981 Mar 19;304(12):685–691. doi: 10.1056/NEJM198103193041201. [DOI] [PubMed] [Google Scholar]
  17. Hughes A., Inkpen P., Sever P. Action of dopamine on isolated human saphenous veins. J Cardiovasc Pharmacol. 1988 Mar;11(3):373–377. doi: 10.1097/00005344-198803000-00016. [DOI] [PubMed] [Google Scholar]
  18. Letts L. G., Piper P. J. The actions of leukotrienes C4 and D4 on guinea-pig isolated hearts. Br J Pharmacol. 1982 May;76(1):169–176. doi: 10.1111/j.1476-5381.1982.tb09203.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maclouf J., de Laclos B. F., Borgeat P. Stimulation of leukotriene biosynthesis in human blood leukocytes by platelet-derived 12-hydroperoxy-icosatetraenoic acid. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6042–6046. doi: 10.1073/pnas.79.19.6042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maltby N. H., Taylor G. W., Ritter J. M., Moore K., Fuller R. W., Dollery C. T. Leukotriene C4 elimination and metabolism in man. J Allergy Clin Immunol. 1990 Jan;85(1 Pt 1):3–9. doi: 10.1016/0091-6749(90)90214-o. [DOI] [PubMed] [Google Scholar]
  22. Mehta P., Mehta J., Lawson D., Krop I., Letts L. G. Leukotrienes potentiate the effects of epinephrine and thrombin on human platelet aggregation. Thromb Res. 1986 Mar 1;41(5):731–738. doi: 10.1016/0049-3848(86)90370-1. [DOI] [PubMed] [Google Scholar]
  23. Michelassi F., Landa L., Hill R. D., Lowenstein E., Watkins W. D., Petkau A. J., Zapol W. M. Leukotriene D4: a potent coronary artery vasoconstrictor associated with impaired ventricular contraction. Science. 1982 Aug 27;217(4562):841–843. doi: 10.1126/science.6808665. [DOI] [PubMed] [Google Scholar]
  24. Nathan C. F. Respiratory burst in adherent human neutrophils: triggering by colony-stimulating factors CSF-GM and CSF-G. Blood. 1989 Jan;73(1):301–306. [PubMed] [Google Scholar]
  25. Nichols W. W., Mehta J. L., Thompson L., Donnelly W. H. Synergistic effects of LTC4 and TxA2 on coronary flow and myocardial function. Am J Physiol. 1988 Jul;255(1 Pt 2):H153–H159. doi: 10.1152/ajpheart.1988.255.1.H153. [DOI] [PubMed] [Google Scholar]
  26. Ohlstein E. H., Nichols A. J. Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle. Circ Res. 1989 Oct;65(4):917–924. doi: 10.1161/01.res.65.4.917. [DOI] [PubMed] [Google Scholar]
  27. Olson N. C., Fleisher L. N. Indomethacin and LY171883 modify porcine cardiopulmonary responses to leukotrienes. Prostaglandins Leukot Essent Fatty Acids. 1989 Mar;35(3):175–182. doi: 10.1016/0952-3278(89)90121-x. [DOI] [PubMed] [Google Scholar]
  28. Piper P. J. Formation and actions of leukotrienes. Physiol Rev. 1984 Apr;64(2):744–761. doi: 10.1152/physrev.1984.64.2.744. [DOI] [PubMed] [Google Scholar]
  29. Roth D. M., Lefer A. M. Studies on the mechanism of leukotriene induced coronary artery constriction. Prostaglandins. 1983 Oct;26(4):573–581. doi: 10.1016/0090-6980(83)90195-8. [DOI] [PubMed] [Google Scholar]
  30. Smedegård G., Hedqvist P., Dahlén S. E., Revenäs B., Hammarström S., Samuelsson B. Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey. Nature. 1982 Jan 28;295(5847):327–329. doi: 10.1038/295327a0. [DOI] [PubMed] [Google Scholar]
  31. Wali F. A. Effects of local anaesthetics on responses of human saphenous vein and bovine coronary artery to neurotransmitters, acetylcholine, noradrenaline and 5-hydroxytryptamine. Gen Pharmacol. 1986;17(4):405–411. doi: 10.1016/0306-3623(86)90182-5. [DOI] [PubMed] [Google Scholar]
  32. Yang Z. H., Diederich D., Schneider K., Siebenmann R., Stulz P., von Segesser L., Turina M., Bühler F. R., Lüscher T. F. Endothelium-derived relaxing factor and protection against contractions induced by histamine and serotonin in the human internal mammary artery and in the saphenous vein. Circulation. 1989 Oct;80(4):1041–1048. doi: 10.1161/01.cir.80.4.1041. [DOI] [PubMed] [Google Scholar]
  33. Yang Z. H., von Segesser L., Bauer E., Stulz P., Turina M., Lüscher T. F. Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein. Circ Res. 1991 Jan;68(1):52–60. doi: 10.1161/01.res.68.1.52. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES