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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Feb;90(2):431–439. doi: 10.1111/j.1476-5381.1987.tb08973.x

Vascular responses to leukotriene B4, C4 and D4 following FPL 55712, indomethacin, saralasin, phentolamine and verapamil in the conscious rat.

J Filep, E Földes-Filep, J C Frölich
PMCID: PMC1916953  PMID: 3030486

Abstract

The pressor and vascular permeability effects of leukotrienes B4 (LTB4), C4 and D4 were investigated in conscious unrestrained rats. Leukotrienes C4 and D4 (3.2-51 nmol kg-1 i.v.) caused an acute dose-dependent elevation of the mean arterial pressure, which was maximal after 2 min and returned to control levels within 14 min. Heart rate was significantly reduced by the higher doses of LTC4 and LTD4. LTB4 (up to a dose of 51 nmol kg-1) was essentially inactive. These effects of LTC4 and LTD4 were abolished by FPL 55712, a putative antagonist of sulphidopeptide leukotrienes and by verapamil, a calcium channel blocker. Indomethacin, phentolamine or saralasin pretreatment failed to modify the pressor response to LTC4 and LTD4. LTC4 and LTD4 furthermore caused an increase in haematocrit values, which was significantly attenuated by FPL 55712, indomethacin and verapamil. The present findings show that the pressor effect of LTC4 and LTD4 is not related to prostanoid release and can be reversed by calcium channel blockade; whereas the effect on vascular permeability seems to require the presence of both cyclo-oxygenase product(s) and calcium.

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Selected References

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  1. Augstein J., Farmer J. B., Lee T. B., Sheard P., Tattersall M. L. Selective inhibitor of slow reacting substance of anaphylaxis. Nat New Biol. 1973 Oct 17;245(146):215–217. doi: 10.1038/newbio245215a0. [DOI] [PubMed] [Google Scholar]
  2. Bach M. K., Brashler J. R., Brooks C. D., Neerken A. J. Slow reacting substances: comparison of some properties of human lung SRS-A and two distinct fractions from ionophore-induced rat mononuclear cell SRS. J Immunol. 1979 Jan;122(1):160–165. [PubMed] [Google Scholar]
  3. Badr K. F., Baylis C., Pfeffer J. M., Pfeffer M. A., Soberman R. J., Lewis R. A., Austen K. F., Corey E. J., Brenner B. M. Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat. Circ Res. 1984 May;54(5):492–499. doi: 10.1161/01.res.54.5.492. [DOI] [PubMed] [Google Scholar]
  4. Casey F. B., Appleby B. J., Buck D. C. Selective inhibition of the lipoxygenase metabolic pathway of arachidonic acid by the SRS-A antagonist, FPL 55712. Prostaglandins. 1983 Jan;25(1):1–11. doi: 10.1016/0090-6980(83)90130-2. [DOI] [PubMed] [Google Scholar]
  5. Cox R. H., Bagshaw R. J. Effects of anesthesia on carotid sinus reflex control of arterial hemodynamics in the dog. Am J Physiol. 1980 Nov;239(5):H681–H691. doi: 10.1152/ajpheart.1980.239.5.H681. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Feigen L. P. Differential effects of leukotrienes C4, D4 and E4 in the canine renal and mesenteric vascular beds. J Pharmacol Exp Ther. 1983 Jun;225(3):682–687. [PubMed] [Google Scholar]
  8. Fejes-Tóth G., Filep J., Mann V. Effect of vasopressin on prostaglandin excretion in conscious dogs. J Physiol. 1983 Nov;344:389–397. doi: 10.1113/jphysiol.1983.sp014947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feuerstein G. Leukotrienes and the cardiovascular system. Prostaglandins. 1984 May;27(5):781–802. doi: 10.1016/0090-6980(84)90015-7. [DOI] [PubMed] [Google Scholar]
  10. Feuerstein G., Zukowska-Grojec Z., Bayorh M., Kopin I. J., Faden A. I. Leukotriene D4-induced hypotension is reversed by thyrotropin-releasing hormone. Prostaglandins. 1983 Nov;26(5):711–724. doi: 10.1016/0090-6980(83)90056-4. [DOI] [PubMed] [Google Scholar]
  11. Fiedler V. B., Mardin M., Abram T. S. Nifedipine on cardiovascular leukotriene D4 actions in the anaesthetized dog. Eur J Pharmacol. 1984 Sep 3;104(1-2):159–164. doi: 10.1016/0014-2999(84)90383-2. [DOI] [PubMed] [Google Scholar]
  12. Filep J., Rigter B., Frölich J. C. Vascular and renal effects of leukotriene C4 in conscious rats. Am J Physiol. 1985 Nov;249(5 Pt 2):F739–F744. doi: 10.1152/ajprenal.1985.249.5.F739. [DOI] [PubMed] [Google Scholar]
  13. Findlay S. R., Leary T. M., Parker C. W., Bloomquist E. I., Scheid C. R. Contractile events induced by LTD4 and histamine in smooth muscle--a function of Ca2+ utilization. Am J Physiol. 1982 Sep;243(3):C133–C139. doi: 10.1152/ajpcell.1982.243.3.C133. [DOI] [PubMed] [Google Scholar]
  14. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  15. Greenwald S. E., Letts L. G., Newman D. L., Piper P. J. Actions of cysteinyl leukotrienes in coronary, femoral and carotid vessels of the pig. Eur J Pharmacol. 1984 Aug 3;103(1-2):107–114. doi: 10.1016/0014-2999(84)90195-x. [DOI] [PubMed] [Google Scholar]
  16. Hammarström S. Leukotrienes. Annu Rev Biochem. 1983;52:355–377. doi: 10.1146/annurev.bi.52.070183.002035. [DOI] [PubMed] [Google Scholar]
  17. Iacopino V. J., Fitzpatrick T. M., Ramwell P. W., Rose J. C., Kot P. A. Cardiovascular responses to leukotriene C4 in the rat. J Pharmacol Exp Ther. 1983 Oct;227(1):244–247. [PubMed] [Google Scholar]
  18. Kohrogi H., Horio S., Ando M., Sugimoto M., Honda I., Araki S. Nifedipine inhibits human bronchial smooth muscle contractions induced by leukotrienes C4 and D4, prostaglandin F2 alpha, and potassium. Am Rev Respir Dis. 1985 Aug;132(2):299–304. doi: 10.1164/arrd.1985.132.2.299. [DOI] [PubMed] [Google Scholar]
  19. Krell R. D., Osborn R., Vickery L., Falcone K., O'Donnell M., Gleason J., Kinzig C., Bryan D. Contraction of isolated airway smooth muscle by synthetic leukotrienes C4 and D4. Prostaglandins. 1981 Sep;22(3):387–409. doi: 10.1016/0090-6980(81)90101-5. [DOI] [PubMed] [Google Scholar]
  20. Krilis S., Lewis R. A., Corey E. J., Austen K. F. Bioconversion of C-6 sulfidopeptide leukotrienes by the responding guinea pig ileum determines the time course of its contraction. J Clin Invest. 1983 Apr;71(4):909–915. doi: 10.1172/JCI110845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Letts L. G., Newman D. L., Greenwald S. E., Piper P. J. Effects of intra-coronary administration of leukotriene D4 in the anaesthetized dog. Prostaglandins. 1983 Oct;26(4):563–572. doi: 10.1016/0090-6980(83)90194-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Murphy R. C., Hammarström S., Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275–4279. doi: 10.1073/pnas.76.9.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Palmer M. R., Mathews W. R., Hoffer B. J., Murphy R. C. Electrophysiological response of cerebellar Purkinje neurons to leukotriene D4 and B4. J Pharmacol Exp Ther. 1981 Oct;219(1):91–96. [PubMed] [Google Scholar]
  27. Pfeffer M. A., Pfeffer J. M., Lewis R. A., Braunwald E., Corey E. J., Austen K. F. Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat. Am J Physiol. 1983 Apr;244(4):H628–H633. doi: 10.1152/ajpheart.1983.244.4.H628. [DOI] [PubMed] [Google Scholar]
  28. Piper P. J., Samhoun M. N. The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat. Prostaglandins. 1981 May;21(5):793–803. doi: 10.1016/0090-6980(81)90236-7. [DOI] [PubMed] [Google Scholar]
  29. Rosenthal A., Pace-Asciak C. R. Potent vasoconstriction of the isolated perfused rat kidney by leukotrienes C4 and D4. Can J Physiol Pharmacol. 1983 Apr;61(4):325–328. doi: 10.1139/y83-049. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Samhoun M. N., Piper P. J. Actions and interactions of lipoxygenase and cyclo-oxygenase products in respiratory and vascular tissues. Prostaglandins Leukot Med. 1984 Jan;13(1):79–87. doi: 10.1016/0262-1746(84)90106-9. [DOI] [PubMed] [Google Scholar]
  32. Sirois P., Kérouac R., Roy S., Borgeat P., Picard S., Rioux F. In vivo effects of leukotriene B4, C4 and D4. Evidence that changes in blood pressure are mediated by prostaglandins. Prostaglandins Med. 1981 Nov;7(5):363–373. doi: 10.1016/0161-4630(81)90025-2. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Ueno A., Tanaka K., Katori M. Possible involvement of thromboxane in bronchoconstrictive and hypertensive effects of LTC4 and LTD4 in guinea pigs. Prostaglandins. 1982 Jun;23(6):865–880. doi: 10.1016/0090-6980(82)90130-7. [DOI] [PubMed] [Google Scholar]
  35. Weichman B. M., Muccitelli R. M., Tucker S. S., Wasserman M. A. Effect of calcium antagonists on leukotriene D4-induced contractions of the guinea-pig trachea and lung parenchyma. J Pharmacol Exp Ther. 1983 May;225(2):310–315. [PubMed] [Google Scholar]
  36. Zerbe R. L., Feuerstein G. Cardiovascular effects of centrally administered vasopressin in conscious and anesthetized rats. Neuropeptides. 1985 Sep;6(5):471–483. doi: 10.1016/0143-4179(85)90146-5. [DOI] [PubMed] [Google Scholar]
  37. Zukowska-Grojec Z., Bayorh M. A., Kopin I. J., Feuerstein G. Leukotriene D4: cardiovascular and sympathetic effects in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. J Pharmacol Exp Ther. 1982 Oct;223(1):183–189. [PubMed] [Google Scholar]

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