Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Mar;93(3):591–600. doi: 10.1111/j.1476-5381.1988.tb10315.x

Some effects of leukotriene D4 on the mechanical properties of the guinea-pig basilar artery.

E Nishiye 1, T Itoh 1, H Kuriyama 1
PMCID: PMC1853825  PMID: 3259445

Abstract

1. The effects of leukotriene D4 (LTD4) on the mechanical properties of smooth muscle cells from the guinea-pig basilar artery were investigated in whole and chemically skinned muscle strips. 2. In strips with an intact endothelium, 5-hydroxytryptamine (5-HT; 10 microM), LTD4 and LTC4 (1 microM), STA2 (1 nM-10 nM) and high K+ (30 mM-128 mM) generated contractions. These comprised an initial phasic and subsequently generated tonic response with different amplitudes. Acetylcholine (ACh, 0.1-10 microM) inhibited and methylene blue (1-10 microM) enhanced the tonic component of these contractions in endothelium-intact muscle strips. In endothelium-denuded tissues, methylene blue had no effect on mechanical responses and ACh produced a further contraction in the presence of LTD4. 3. When the endothelium was removed, the amplitude of contractions induced by all tested stimulants markedly increased. In intact muscle strips, the order of potency for the production of a maximum response was; 128 mM K+ greater than STA2 greater than LTD4 = LTC4 = 5-HT. Following removal of the endothelium; STA2 greater than 128 mM K+ greater than LTD4 = LTC4 much greater than 5-HT. 4. In endothelium-denuded strips, the selective LTD4 antagonists, ONO-RS-411 and FPL 55712 inhibited the LTD4-induced contraction. In contrast, guanethidine, prazosin, yohimbine, atropine and mepyramine had no effect. Indomethacin and a thromboxane A2(TXA2) antagonist, ONO-3708 also had no effect on LTD4-induced contractions in endothelium-denuded strips. 5. In endothelium-denuded strips, nifedipine inhibited the tonic contraction induced by LTD4 but not the phasic component. In Ca2+-free solution containing 2 mM EGTA, LTD4 produced only the phasic contractions. 6. In saponin-treated chemically skinned muscle strips, LTD4 had no effect on either the pCa-tension relationship or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5-triphosphate released Ca2+ from the stores and 1,2-diolein, an activator of protein kinase C, enhanced the contractions induced by 0.3 microM Ca2+. 7. It was concluded that LTD4 acts on both the endothelium and on the smooth muscle cells of the guinea-pig basilar artery. It stimulates the release of endothelium-derived relaxing factor (EDRF) which tends to inhibit the LTD4-induced contraction. It also interacts with receptors on the smooth muscle and produces a contraction as a result of an increase in both voltage-dependent and receptor-activated Ca2+ influx and, in part, the release of Ca2+ from cellular storage sites.

Full text

PDF
596

Selected References

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

  1. Abdel-Latif A. A. Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers. Pharmacol Rev. 1986 Sep;38(3):227–272. [PubMed] [Google Scholar]
  2. Bean B. P., Sturek M., Puga A., Hermsmeyer K. Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs. Circ Res. 1986 Aug;59(2):229–235. doi: 10.1161/01.res.59.2.229. [DOI] [PubMed] [Google Scholar]
  3. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  4. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  5. Borgeat P., Samuelsson B. Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem. 1979 Aug 25;254(16):7865–7869. [PubMed] [Google Scholar]
  6. Busija D. W., Leffler C. W., Beasley D. G. Effects of leukotrienes C4, D4, and E4 on cerebral arteries of newborn pigs. Pediatr Res. 1986 Oct;20(10):973–976. doi: 10.1203/00006450-198610000-00016. [DOI] [PubMed] [Google Scholar]
  7. Furchgott R. F. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. doi: 10.1146/annurev.pa.24.040184.001135. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Hashimoto T., Hirata M., Ito Y. A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle. Br J Pharmacol. 1985 Sep;86(1):191–199. doi: 10.1111/j.1476-5381.1985.tb09449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hedqvist P., Dahlén S. E., Gustafsson L., Hammarström S., Samuelsson B. Biological profile of leukotrienes C4 and D4. Acta Physiol Scand. 1980 Nov;110(3):331–333. doi: 10.1111/j.1748-1716.1980.tb06676.x. [DOI] [PubMed] [Google Scholar]
  12. Hughes J. T., Schianchi P. M. Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg. 1978 Apr;48(4):515–525. doi: 10.3171/jns.1978.48.4.0515. [DOI] [PubMed] [Google Scholar]
  13. Högestätt E. D., Uski T. K. Actions of some prostaglandins and leukotrienes on rat cerebral and mesenteric arteries. Gen Pharmacol. 1987;18(2):111–117. doi: 10.1016/0306-3623(87)90235-7. [DOI] [PubMed] [Google Scholar]
  14. Itoh T., Kajiwara M., Kitamura K., Kuriyama H. Roles of stored calcium on the mechanical response evoked in smooth muscle cells of the porcine coronary artery. J Physiol. 1982 Jan;322:107–125. doi: 10.1113/jphysiol.1982.sp014026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Itoh T., Kanmura Y., Kuriyama H., Sasaguri T. Nitroglycerine- and isoprenaline-induced vasodilatation: assessment from the actions of cyclic nucleotides. Br J Pharmacol. 1985 Feb;84(2):393–406. doi: 10.1111/j.1476-5381.1985.tb12923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Itoh T., Kuriyama H., Suzuki H. Differences and similarities in the noradrenaline- and caffeine-induced mechanical responses in the rabbit mesenteric artery. J Physiol. 1983 Apr;337:609–629. doi: 10.1113/jphysiol.1983.sp014645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Itoh T., Kuriyama H., Suzuki H. Excitation--contraction coupling in smooth muscle cells of the guinea-pig mesenteric artery. J Physiol. 1981 Dec;321:513–535. doi: 10.1113/jphysiol.1981.sp014000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kamitani T., Little M. H., Ellis E. F. Effect of leukotrienes, 12-HETE, histamine, bradykinin, and 5-hydroxytryptamine on in vivo rabbit cerebral arteriolar diameter. J Cereb Blood Flow Metab. 1985 Dec;5(4):554–559. doi: 10.1038/jcbfm.1985.83. [DOI] [PubMed] [Google Scholar]
  19. Kamm K. E., Stull J. T. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol. 1985;25:593–620. doi: 10.1146/annurev.pa.25.040185.003113. [DOI] [PubMed] [Google Scholar]
  20. Kanmura Y., Itoh T., Kuriyama H. Mechanisms of vasoconstriction induced by 9,11-epithio-11,12-methano-thromboxane A2 in the rabbit coronary artery. Circ Res. 1987 Mar;60(3):402–409. doi: 10.1161/01.res.60.3.402. [DOI] [PubMed] [Google Scholar]
  21. Kito G., Okuda H., Ohkawa S., Terao S., Kikuchi K. Contractile activities of leukotrienes C4 and D4 on vascular strips from rabbits. Life Sci. 1981 Sep 28;29(13):1325–1332. doi: 10.1016/0024-3205(81)90675-5. [DOI] [PubMed] [Google Scholar]
  22. Kiwak K. J., Moskowitz M. A., Levine L. Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury. J Neurosurg. 1985 Jun;62(6):865–869. doi: 10.3171/jns.1985.62.6.0865. [DOI] [PubMed] [Google Scholar]
  23. Kobayashi S., Kanaide H., Nakamura M. Cytosolic-free calcium transients in cultured vascular smooth muscle cells: microfluorometric measurements. Science. 1985 Aug 9;229(4713):553–556. doi: 10.1126/science.3927484. [DOI] [PubMed] [Google Scholar]
  24. Kopia G. A., Valocik R. E., Torphy T. J., Cieslinksi L. B., Sarau H. M., Foley J. J., Wasserman M. A. Inhibition of leukotriene D4-induced coronary vasoconstriction by leukotriene antagonists in the anesthetized dog. J Pharmacol Exp Ther. 1987 Apr;241(1):174–180. [PubMed] [Google Scholar]
  25. Liszczak T. M., Varsos V. G., Black P. M., Kistler J. P., Zervas N. T. Cerebral arterial constriction after experimental subarachnoid hemorrhage is associated with blood components within the arterial wall. J Neurosurg. 1983 Jan;58(1):18–26. doi: 10.3171/jns.1983.58.1.0018. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Murad F. Cyclic guanosine monophosphate as a mediator of vasodilation. J Clin Invest. 1986 Jul;78(1):1–5. doi: 10.1172/JCI112536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nakamura T., Suzuki N., Hishinuma I., Ishikawa Y., Sasaki T., Asano T. Appearance of 5-hydroxy eicosatetraenoic acid in cerebrospinal fluid after subarachnoid haemorrhage. Med Biol. 1984;62(2):125–128. [PubMed] [Google Scholar]
  29. Obata T., Katsube N., Miyamoto T., Toda M., Okegawa T., Nakai H., Kosuge S., Konno M., Arai Y., Kawasaki A. New antagonists of leukotrienes: ONO-RS-411 and ONO-RS-347. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:229–231. [PubMed] [Google Scholar]
  30. Piper P. J., Stewart A. G. Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet-activating factor is mediated by leukotriene C4. Br J Pharmacol. 1986 Jul;88(3):595–605. doi: 10.1111/j.1476-5381.1986.tb10240.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rapoport R. M., Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983 Mar;52(3):352–357. doi: 10.1161/01.res.52.3.352. [DOI] [PubMed] [Google Scholar]
  32. Rosenblum W. I. Constricting effect of leukotrienes on cerebral arterioles of mice. Stroke. 1985 Mar-Apr;16(2):262–263. doi: 10.1161/01.str.16.2.262. [DOI] [PubMed] [Google Scholar]
  33. Rouzer C. A., Scott W. A., Cohn Z. A., Blackburn P., Manning J. M. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. doi: 10.1073/pnas.77.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sasaguri T., Itoh T., Hirata M., Kitamura K., Kuriyama H. Regulation of coronary artery tone in relation to the activation of signal transductors that regulate calcium homeostasis. J Am Coll Cardiol. 1987 May;9(5):1167–1175. doi: 10.1016/s0735-1097(87)80322-4. [DOI] [PubMed] [Google Scholar]
  35. Secrest R. J., Olsen E. J., Chapnick B. M. Leukotriene D4 relaxes canine renal and superior mesenteric arteries. Circ Res. 1985 Aug;57(2):323–329. doi: 10.1161/01.res.57.2.323. [DOI] [PubMed] [Google Scholar]
  36. Shimizu T., Izumi T., Seyama Y., Tadokoro K., Rådmark O., Samuelsson B. Characterization of leukotriene A4 synthase from murine mast cells: evidence for its identity to arachidonate 5-lipoxygenase. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4175–4179. doi: 10.1073/pnas.83.12.4175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Suematsu E., Hirata M., Hashimoto T., Kuriyama H. Inositol 1,4,5-trisphosphate releases Ca2+ from intracellular store sites in skinned single cells of porcine coronary artery. Biochem Biophys Res Commun. 1984 Apr 30;120(2):481–485. doi: 10.1016/0006-291x(84)91279-8. [DOI] [PubMed] [Google Scholar]
  38. Suematsu E., Hirata M., Kuriyama H. Effects of cAMP- and cGMP-dependent protein kinases, and calmodulin on Ca2+ uptake by highly purified sarcolemmal vesicles of vascular smooth muscle. Biochim Biophys Acta. 1984 Jun 13;773(1):83–90. doi: 10.1016/0005-2736(84)90552-2. [DOI] [PubMed] [Google Scholar]
  39. Suzuki N., Nakamura T., Imabayashi S., Ishikawa Y., Sasaki T., Asano T. Identification of 5-hydroxy eicosatetraenoic acid in cerebrospinal fluid after subarachnoid hemorrhage. J Neurochem. 1983 Oct;41(4):1186–1189. doi: 10.1111/j.1471-4159.1983.tb09071.x. [DOI] [PubMed] [Google Scholar]
  40. Tagari P., Du Boulay G. H., Aitken V., Boullin D. J. Leukotriene D4 and the cerebral vasculature in vivo and in vitro. Prostaglandins Leukot Med. 1983 Jul;11(3):281–297. doi: 10.1016/0262-1746(83)90041-0. [DOI] [PubMed] [Google Scholar]
  41. Yokota M., Tani E., Maeda Y., Kokubu K. Effect of 5-lipoxygenase inhibitor on experimental delayed cerebral vasospasm. Stroke. 1987 Mar-Apr;18(2):512–518. doi: 10.1161/01.str.18.2.512. [DOI] [PubMed] [Google Scholar]
  42. von Holst H., Granström E., Hammarström S., Samuelsson B., Steiner L. Effect of leucotrienes C4, D4, prostacyclin and thromboxane A2 on isolated human cerebral arteries. Acta Neurochir (Wien) 1982;62(3-4):177–185. doi: 10.1007/BF01403622. [DOI] [PubMed] [Google Scholar]

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

RESOURCES