Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Dec;113(4):1257–1262. doi: 10.1111/j.1476-5381.1994.tb17133.x

Block of endothelin-1-induced release of thromboxane A2 from the guinea pig lung and nitric oxide from the rabbit kidney by a selective ETB receptor antagonist, BQ-788.

P D'Orléans-Juste 1, A Claing 1, S Télémaque 1, M C Maurice 1, M Yano 1, J P Gratton 1
PMCID: PMC1510539  PMID: 7889281

Abstract

1. The present study characterizes the receptors responsible for endothelin-1-induced release of thromboxane A2 from the guinea pig lung and of endothelium-derived nitric oxide from the rabbit perfused kidney, by the use of the selective ETA receptor antagonist, BQ-123, and a novel selective ETB receptor antagonist, BQ-788. 2. In the guinea pig perfused lung, endothelin-1 (ET-1) (5 nM) induced a marked increase of thromboxane A2 which was reduced by 17 +/- 5.0, 70 +/- 1.0 and 93 +/- 1.2% by BQ-788 infused at concentrations of 1, 5 and 10 nM respectively. In contrast, BQ-123 (0.1 and 1.0 microM) had little or no effect on the ET-1-induced release of thromboxane A2. 3. In the same perfused model, the selective ETB agonist, IRL 1620 (50 nM), stimulated the release of thromboxane A2, but not prostacyclin. The eicosanoid-releasing properties of IRL 1620 were abolished by BQ-788 at 10 nM, yet were unaffected by BQ-123 (1 microM). 4. In the rabbit perfused kidney, BQ-788 (10 nM) potentiated the increase of perfusion pressure induced by endothelin-1 (1, 5 and 10 nM) by approximately 90%, but not that induced by angiotensin II (1 microM). Furthermore, the selective ETB receptor antagonist did not reduce the release of prostacyclin triggered by either peptide. 5. In another series of experiments, pretreatment of the perfused kidney with a nitric oxide synthase inhibitor, L-NAME (100 microM), potentiated the pressor responses to both endothelin-1 and angiotensin II. Under L-NAME treatment, BQ-788 did not further potentiate the pressor response to endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1257

Selected References

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

  1. Battistini B., Warner T. D., Fournier A., Vane J. R. Characterization of ETB receptors mediating contractions induced by endothelin-1 or IRL 1620 in guinea-pig isolated airways: effects of BQ-123, FR139317 or PD 145065. Br J Pharmacol. 1994 Apr;111(4):1009–1016. doi: 10.1111/j.1476-5381.1994.tb14844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clozel M., Breu V., Burri K., Cassal J. M., Fischli W., Gray G. A., Hirth G., Löffler B. M., Müller M., Neidhart W. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature. 1993 Oct 21;365(6448):759–761. doi: 10.1038/365759a0. [DOI] [PubMed] [Google Scholar]
  3. D'Orléans-Juste P., Claing A., Warner T. D., Yano M., Télémaque S. Characterization of receptors for endothelins in the perfused arterial and venous mesenteric vasculatures of the rat. Br J Pharmacol. 1993 Oct;110(2):687–692. doi: 10.1111/j.1476-5381.1993.tb13866.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. D'Orléans-Juste P., Télémaque S., Claing A., Ihara M., Yano M. Human big-endothelin-1 and endothelin-1 release prostacyclin via the activation of ET1 receptors in the rat perfused lung. Br J Pharmacol. 1992 Apr;105(4):773–775. doi: 10.1111/j.1476-5381.1992.tb09055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Denton K. M., Anderson W. P. Vascular actions of endothelin in the rabbit kidney. Clin Exp Pharmacol Physiol. 1990 Dec;17(12):861–872. doi: 10.1111/j.1440-1681.1990.tb01289.x. [DOI] [PubMed] [Google Scholar]
  6. Ehrenreich H., Anderson R. W., Fox C. H., Rieckmann P., Hoffman G. S., Travis W. D., Coligan J. E., Kehrl J. H., Fauci A. S. Endothelins, peptides with potent vasoactive properties, are produced by human macrophages. J Exp Med. 1990 Dec 1;172(6):1741–1748. doi: 10.1084/jem.172.6.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hay D. W., Luttmann M. A., Hubbard W. C., Undem B. J. Endothelin receptor subtypes in human and guinea-pig pulmonary tissues. Br J Pharmacol. 1993 Nov;110(3):1175–1183. doi: 10.1111/j.1476-5381.1993.tb13938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ihara M., Noguchi K., Saeki T., Fukuroda T., Tsuchida S., Kimura S., Fukami T., Ishikawa K., Nishikibe M., Yano M. Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci. 1992;50(4):247–255. doi: 10.1016/0024-3205(92)90331-i. [DOI] [PubMed] [Google Scholar]
  9. Ishikawa K., Ihara M., Noguchi K., Mase T., Mino N., Saeki T., Fukuroda T., Fukami T., Ozaki S., Nagase T. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4892–4896. doi: 10.1073/pnas.91.11.4892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaw S., Hecker M., Vane J. R. The two-step conversion of big endothelin 1 to endothelin 1 and degradation of endothelin 1 by subcellular fractions from human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6886–6890. doi: 10.1073/pnas.89.15.6886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. King A. J., Brenner B. M., Anderson S. Endothelin: a potent renal and systemic vasoconstrictor peptide. Am J Physiol. 1989 Jun;256(6 Pt 2):F1051–F1058. doi: 10.1152/ajprenal.1989.256.6.F1051. [DOI] [PubMed] [Google Scholar]
  12. Löffler B. M., Breu V., Clozel M. Effect of different endothelin receptor antagonists and of the novel non-peptide antagonist Ro 46-2005 on endothelin levels in rat plasma. FEBS Lett. 1993 Oct 25;333(1-2):108–110. doi: 10.1016/0014-5793(93)80384-7. [DOI] [PubMed] [Google Scholar]
  13. Ninomiya H., Yu X. Y., Hasegawa S., Spannhake E. W. Endothelin-1 induces stimulation of prostaglandin synthesis in cells obtained from canine airways by bronchoalveolar lavage. Prostaglandins. 1992 May;43(5):401–411. doi: 10.1016/0090-6980(92)90124-c. [DOI] [PubMed] [Google Scholar]
  14. Noguchi K., Noguchi Y., Hirose H., Nishikibe M., Ihara M., Ishikawa K., Yano M. Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs. Eur J Pharmacol. 1993 Mar 16;233(1):47–51. doi: 10.1016/0014-2999(93)90347-k. [DOI] [PubMed] [Google Scholar]
  15. Rae G. A., Trybulec M., de Nucci G., Vane J. R. Endothelin-1 releases eicosanoids from rabbit isolated perfused kidney and spleen. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S89–S102. doi: 10.1097/00005344-198900135-00022. [DOI] [PubMed] [Google Scholar]
  16. Sakurai T., Yanagisawa M., Takuwa Y., Miyazaki H., Kimura S., Goto K., Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20;348(6303):732–735. doi: 10.1038/348732a0. [DOI] [PubMed] [Google Scholar]
  17. Salmon J. A. A radioimmunoassay for 6-keto-prostaglandin F1alpha. Prostaglandins. 1978 Mar;15(3):383–397. doi: 10.1016/0090-6980(78)90122-3. [DOI] [PubMed] [Google Scholar]
  18. Sessa W. C., Kaw S., Hecker M., Vane J. R. The biosynthesis of endothelin-1 by human polymorphonuclear leukocytes. Biochem Biophys Res Commun. 1991 Jan 31;174(2):613–618. doi: 10.1016/0006-291x(91)91461-k. [DOI] [PubMed] [Google Scholar]
  19. Télémaque S., Gratton J. P., Claing A., D'Orléans-Juste P. Endothelin-1 induces vasoconstriction and prostacyclin release via the activation of endothelin ETA receptors in the perfused rabbit kidney. Eur J Pharmacol. 1993 Jun 24;237(2-3):275–281. doi: 10.1016/0014-2999(93)90279-q. [DOI] [PubMed] [Google Scholar]
  20. Télémaque S., Lemaire D., Claing A., D'Orléans-Juste P. Phosphoramidon-sensitive effects of big endothelins in the perfused rabbit kidney. Hypertension. 1992 Oct;20(4):518–523. doi: 10.1161/01.hyp.20.4.518. [DOI] [PubMed] [Google Scholar]
  21. Warner T. D., de Nucci G., Vane J. R. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol. 1989 Jan 17;159(3):325–326. doi: 10.1016/0014-2999(89)90167-2. [DOI] [PubMed] [Google Scholar]
  22. Whittle B. J., Lopez-Belmonte J., Rees D. D. Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br J Pharmacol. 1989 Oct;98(2):646–652. doi: 10.1111/j.1476-5381.1989.tb12639.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Whittle B. J., Payne A. N., Esplugues J. V. Cardiopulmonary and gastric ulcerogenic actions of endothelin-1 in the guinea pig and rat. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S103–S123. doi: 10.1097/00005344-198900135-00026. [DOI] [PubMed] [Google Scholar]
  24. de Nucci G., Thomas R., D'Orleans-Juste P., Antunes E., Walder C., Warner T. D., Vane J. R. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797–9800. doi: 10.1073/pnas.85.24.9797. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES