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. 1993 Jul;109(3):637–644. doi: 10.1111/j.1476-5381.1993.tb13620.x

Induction by endothelin-1 of epithelium-dependent relaxation of guinea-pig trachea in vitro: role for nitric oxide.

J G Filep 1, B Battistini 1, P Sirois 1
PMCID: PMC2175613  PMID: 8102933

Abstract

1. The purpose of the present experiments was to study the underlying mechanisms responsible for the relaxant action of endothelin-1 (ET-1) in the guinea-pig trachea in vitro. 2. In tracheal strips precontracted (60-70% of the maximum) with carbachol, ET-1 (1-100 nM) evoked slowly developing concentration-dependent relaxations. Preincubation of the tissues with the thromboxane A2/prostaglandin H2 receptor antagonist, BM 13505 (5 microM) significantly potentiated the relaxant response to ET-1. 3. Removal of the epithelium changed the response of precontracted tracheal preparations to ET-1 from a relaxation to a sustained contraction. 4. ET-1-induced relaxations were abolished by methylene blue (10 microM) and were almost completely attenuated by oxyhaemoglobin (5 microM) and NG-monomethyl-L-arginine (L-NMMA, 100 microM), an inhibitor of nitric oxide synthesis, but were not altered by indomethacin (10 microM). 5. In tracheal strips under passive tension, ET-1 (1-100 nM) elicited dose-dependent contractions. The sensitivity of tissues to ET-1 was significantly enhanced by removal of the epithelium (apparent EC50 values were 28.1 +/- 4.1 and 12.5 +/- 0.8 nM in intact and rubbed trachea, respectively, n = 7, P < 0.01). 6. Preincubation of intact tracheal strips with methylene blue, oxyhaemoglobin or L-NMMA did not mimic the effect of epithelium removal on ET-1-induced contractions. 7. There was a concentration-dependent increase in thromboxane A2 but not in PGE2 and prostacyclin release from intact tracheal strips following stimulation with ET-1 (5-100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Barnes P. J., Cuss F. M., Palmer J. B. The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol. 1985 Nov;86(3):685–691. doi: 10.1111/j.1476-5381.1985.tb08946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battistini B., Filep J., Sirois P. Potent thromboxane-mediated in vitro bronchoconstrictor effect of endothelin in the guinea-pig. Eur J Pharmacol. 1990 Mar 13;178(1):141–142. doi: 10.1016/0014-2999(90)94808-b. [DOI] [PubMed] [Google Scholar]
  3. Black P. N., Ghatei M. A., Takahashi K., Bretherton-Watt D., Krausz T., Dollery C. T., Bloom S. R. Formation of endothelin by cultured airway epithelial cells. FEBS Lett. 1989 Sep 11;255(1):129–132. doi: 10.1016/0014-5793(89)81075-0. [DOI] [PubMed] [Google Scholar]
  4. Bramley A. M., Samhoun M. N., Piper P. J. The role of the epithelium in modulating the responses of guinea-pig trachea induced by bradykinin in vitro. Br J Pharmacol. 1990 Apr;99(4):762–766. doi: 10.1111/j.1476-5381.1990.tb13003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brunelleschi S., Haye-Legrand I., Labat C., Norel X., Benveniste J., Brink C. Platelet-activating factor-acether-induced relaxation of guinea pig airway muscle: role of prostaglandin E2 and the epithelium. J Pharmacol Exp Ther. 1987 Oct;243(1):356–363. [PubMed] [Google Scholar]
  6. Dupuy P. M., Shore S. A., Drazen J. M., Frostell C., Hill W. A., Zapol W. M. Bronchodilator action of inhaled nitric oxide in guinea pigs. J Clin Invest. 1992 Aug;90(2):421–428. doi: 10.1172/JCI115877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farmer S. G., Hay D. W., Raeburn D., Fedan J. S. Relaxation of guinea-pig tracheal smooth muscle to arachidonate is converted to contraction following epithelium removal. Br J Pharmacol. 1987 Sep;92(1):231–236. doi: 10.1111/j.1476-5381.1987.tb11316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandes L. B., Goldie R. G. Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF). Br J Pharmacol. 1990 Jul;100(3):614–618. doi: 10.1111/j.1476-5381.1990.tb15855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fernandes L. B., Paterson J. W., Goldie R. G. Co-axial bioassay of a smooth muscle relaxant factor released from guinea-pig tracheal epithelium. Br J Pharmacol. 1989 Jan;96(1):117–124. doi: 10.1111/j.1476-5381.1989.tb11791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Filep J. G., Battistini B., Sirois P. Endothelin induces thromboxane release and contraction of isolated guinea-pig airways. Life Sci. 1990;47(20):1845–1850. doi: 10.1016/0024-3205(90)90287-2. [DOI] [PubMed] [Google Scholar]
  11. Filep J. G., Battistini B., Sirois P. Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release. Br J Pharmacol. 1991 Jul;103(3):1633–1640. doi: 10.1111/j.1476-5381.1991.tb09840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flavahan N. A., Aarhus L. L., Rimele T. J., Vanhoutte P. M. Respiratory epithelium inhibits bronchial smooth muscle tone. J Appl Physiol (1985) 1985 Mar;58(3):834–838. doi: 10.1152/jappl.1985.58.3.834. [DOI] [PubMed] [Google Scholar]
  13. Gold M. E., Wood K. S., Byrns R. E., Fukuto J., Ignarro L. J. NG-methyl-L-arginine causes endothelium-dependent contraction and inhibition of cyclic GMP formation in artery and vein. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4430–4434. doi: 10.1073/pnas.87.12.4430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldie R. G., Papadimitriou J. M., Paterson J. W., Rigby P. J., Self H. M., Spina D. Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists. Br J Pharmacol. 1986 Jan;87(1):5–14. doi: 10.1111/j.1476-5381.1986.tb10150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grunstein M. M., Chuang S. T., Schramm C. M., Pawlowski N. A. Role of endothelin 1 in regulating rabbit airway contractility. Am J Physiol. 1991 Feb;260(2 Pt 1):L75–L82. doi: 10.1152/ajplung.1991.260.2.L75. [DOI] [PubMed] [Google Scholar]
  16. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  17. Güc M. O., Ilhan M., Kayaalp S. O. The rat anococcygeus muscle is a convenient bioassay organ for the airway epithelium-derived relaxant factor. Eur J Pharmacol. 1988 Apr 13;148(3):405–409. doi: 10.1016/0014-2999(88)90119-7. [DOI] [PubMed] [Google Scholar]
  18. Hay D. W., Farmer S. G., Raeburn D., Muccitelli R. M., Wilson K. A., Fedan J. S. Differential effects of epithelium removal on the responsiveness of guinea-pig tracheal smooth muscle to bronchoconstrictors. Br J Pharmacol. 1987 Oct;92(2):381–388. doi: 10.1111/j.1476-5381.1987.tb11334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hay D. W. Guinea-pig tracheal epithelium and endothelin. Eur J Pharmacol. 1989 Nov 21;171(2-3):241–245. doi: 10.1016/0014-2999(89)90114-3. [DOI] [PubMed] [Google Scholar]
  20. Hay D. W. Mechanism of endothelin-induced contraction in guinea-pig trachea: comparison with rat aorta. Br J Pharmacol. 1990 Jun;100(2):383–392. doi: 10.1111/j.1476-5381.1990.tb15814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hay D. W., Muccitelli R. M., Page C. P., Spina D. Correlation between airway epithelium-induced relaxation of rat aorta in the co-axial bioassay and cyclic nucleotide levels. Br J Pharmacol. 1992 Apr;105(4):954–958. doi: 10.1111/j.1476-5381.1992.tb09084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Henry P. J., Rigby P. J., Self G. J., Preuss J. M., Goldie R. G. Relationship between endothelin-1 binding site densities and constrictor activities in human and animal airway smooth muscle. Br J Pharmacol. 1990 Aug;100(4):786–792. doi: 10.1111/j.1476-5381.1990.tb14093.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hille R., Palmer G., Olson J. S. Chain equivalence in reaction of nitric oxide with hemoglobin. J Biol Chem. 1977 Jan 10;252(1):403–405. [PubMed] [Google Scholar]
  24. Holroyde M. C. The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br J Pharmacol. 1986 Mar;87(3):501–507. doi: 10.1111/j.1476-5381.1986.tb10192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ignarro L. J. Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res. 1989 Jul;65(1):1–21. doi: 10.1161/01.res.65.1.1. [DOI] [PubMed] [Google Scholar]
  26. Ignarro L. J., Burke T. M., Wood K. S., Wolin M. S., Kadowitz P. J. Association between cyclic GMP accumulation and acetylcholine-elicited relaxation of bovine intrapulmonary artery. J Pharmacol Exp Ther. 1984 Mar;228(3):682–690. [PubMed] [Google Scholar]
  27. Ilhan M., Sahin I. Tracheal epithelium releases a vascular smooth muscle relaxant factor: demonstration by bioassay. Eur J Pharmacol. 1986 Nov 19;131(2-3):293–296. doi: 10.1016/0014-2999(86)90586-8. [DOI] [PubMed] [Google Scholar]
  28. Jansen A., Drazen J., Osborne J. A., Brown R., Loscalzo J., Stamler J. S. The relaxant properties in guinea pig airways of S-nitrosothiols. J Pharmacol Exp Ther. 1992 Apr;261(1):154–160. [PubMed] [Google Scholar]
  29. Kannan M. S., Johnson D. E. Nitric oxide mediates the neural nonadrenergic, noncholinergic relaxation of pig tracheal smooth muscle. Am J Physiol. 1992 Apr;262(4 Pt 1):L511–L514. doi: 10.1152/ajplung.1992.262.4.L511. [DOI] [PubMed] [Google Scholar]
  30. Laitinen L. A., Heino M., Laitinen A., Kava T., Haahtela T. Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis. 1985 Apr;131(4):599–606. doi: 10.1164/arrd.1985.131.4.599. [DOI] [PubMed] [Google Scholar]
  31. Li C. G., Rand M. J. Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. Br J Pharmacol. 1991 Jan;102(1):91–94. doi: 10.1111/j.1476-5381.1991.tb12137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Maggi C. A., Patacchini R., Giuliani S., Meli A. Potent contractile effect of endothelin in isolated guinea-pig airways. Eur J Pharmacol. 1989 Jan 24;160(1):179–182. doi: 10.1016/0014-2999(89)90670-5. [DOI] [PubMed] [Google Scholar]
  33. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  34. McCord J. M., Fridovich I. The utility of superoxide dismutase in studying free radical reactions. II. The mechanism of the mediation of cytochrome c reduction by a variety of electron carriers. J Biol Chem. 1970 Mar 25;245(6):1374–1377. [PubMed] [Google Scholar]
  35. Mehta J. L., Lawson D. L., Yang B. C., Mehta P., Nichols W. W. Modulation of vascular tone by endothelin-1: role of preload, endothelial integrity and concentration of endothelin-1. Br J Pharmacol. 1992 May;106(1):127–132. doi: 10.1111/j.1476-5381.1992.tb14304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Miller V. M., Vanhoutte P. M. Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins? Am J Physiol. 1989 Dec;257(6 Pt 2):H1910–H1916. doi: 10.1152/ajpheart.1989.257.6.H1910. [DOI] [PubMed] [Google Scholar]
  37. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  38. Raeburn D. Eicosanoids, epithelium and airway reactivity. Gen Pharmacol. 1990;21(1):11–16. doi: 10.1016/0306-3623(90)90587-c. [DOI] [PubMed] [Google Scholar]
  39. Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rozengurt N., Springall D. R., Polak J. M. Localization of endothelin-like immunoreactivity in airway epithelium of rats and mice. J Pathol. 1990 Jan;160(1):5–8. doi: 10.1002/path.1711600104. [DOI] [PubMed] [Google Scholar]
  42. Rubanyi G. M., Vanhoutte P. M. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol. 1986 May;250(5 Pt 2):H822–H827. doi: 10.1152/ajpheart.1986.250.5.H822. [DOI] [PubMed] [Google Scholar]
  43. Svenssen J., Strandberg K., Tuvemo T., Hamberg M. Thromboxane A2: effects on airway and vascular smooth muscle. Prostaglandins. 1977 Sep;14(3):425–436. doi: 10.1016/0090-6980(77)90258-1. [DOI] [PubMed] [Google Scholar]
  44. Turner N. C., Power R. F., Polak J. M., Bloom S. R., Dollery C. T. Endothelin-induced contractions of tracheal smooth muscle and identification of specific endothelin binding sites in the trachea of the rat. Br J Pharmacol. 1989 Oct;98(2):361–366. doi: 10.1111/j.1476-5381.1989.tb12605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Uchida Y., Ninomiya H., Saotome M., Nomura A., Ohtsuka M., Yanagisawa M., Goto K., Masaki T., Hasegawa S. Endothelin, a novel vasoconstrictor peptide, as potent bronchoconstrictor. Eur J Pharmacol. 1988 Sep 13;154(2):227–228. doi: 10.1016/0014-2999(88)90106-9. [DOI] [PubMed] [Google Scholar]
  46. Undem B. J., Raible D. G., Adkinson N. F., Jr, Adams G. K., 3rd Effect of removal of epithelium on antigen-induced smooth muscle contraction and mediator release from guinea pig isolated trachea. J Pharmacol Exp Ther. 1988 Feb;244(2):659–665. [PubMed] [Google Scholar]
  47. Vanhoutte P. M. Epithelium-derived relaxing factor(s) and bronchial reactivity. Am Rev Respir Dis. 1988 Dec;138(6 Pt 2):S24–S30. doi: 10.1164/ajrccm/138.6_Pt_2.S24. [DOI] [PubMed] [Google Scholar]
  48. Vargas H. M., Ignarro L. J., Chaudhuri G. Physiological release of nitric oxide is dependent on the level of vascular tone. Eur J Pharmacol. 1990 Nov 13;190(3):393–397. doi: 10.1016/0014-2999(90)94204-b. [DOI] [PubMed] [Google Scholar]
  49. White S. R., Hathaway D. P., Umans J. G., Tallet J., Abrahams C., Leff A. R. Epithelial modulation of airway smooth muscle response to endothelin-1. Am Rev Respir Dis. 1991 Aug;144(2):373–378. doi: 10.1164/ajrccm/144.2.373. [DOI] [PubMed] [Google Scholar]
  50. 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]

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