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. 1993 Jun;109(2):530–534. doi: 10.1111/j.1476-5381.1993.tb13602.x

Mediation of endothelin-1-induced inhibition of platelet aggregation via the ETB receptor.

L McMurdo 1, P S Lidbury 1, C Thiemermann 1, J R Vane 1
PMCID: PMC2175682  PMID: 8358553

Abstract

1. The effects of FR139317 (ETA antagonist) or PD145065 (non-selective ETA/ETB antagonist) on endothelin-1 (ET-1)-induced changes in blood pressure and inhibition of ex vivo platelet aggregation were investigated in the anaesthetized rabbit. 2. ET-1 (1 nmol kg-1, i.a. bolus) caused a sustained increase in mean arterial pressure (MAP) (peak increase 47 +/- 5 mmHg, n = 8). Intravenous infusion of FR139317 at 0.2 (n = 4) or 0.6 mg kg-1 min-1 (n = 4) inhibited the ET-1 pressor response by 83 or 89%, respectively. Infusion of PD145065 at 0.2 (n = 4) or 0.6 mg kg-1 min-1 (n = 4) inhibited the ET-1-induced increase in MAP by 79 or 75%, respectively. 3. The transient depressor response (-16 +/- 3 mmHg) which preceded the rise in blood pressure induced by ET-1 (1 nmol kg-1, i.a., n = 8) was enhanced by an intravenous infusion of FR139317 (0.6 mg kg-1 min-1) to -35 +/- 5 mmHg (P < 0.05, n = 4). This enhancement was abolished by indomethacin (5 mg kg-1, i.v.) pretreatment (-17 +/- 1 mmHg, n = 4). PD145065 (0.2 mg kg-1 min-1, i.v.) attenuated the ET-1-induced fall in blood pressure to -9 +/- 1 mmHg (n = 4), while a higher dose of this antagonist (0.6 mg kg-1 min-1, i.v.) completely abolished the ET-1-mediated depressor response. 4. ET-1 (1 nmol kg-1, n = 8) inhibited ex vivo platelet aggregation by 96% at 5 min after injection of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Arai H., Hori S., Aramori I., Ohkubo H., Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990 Dec 20;348(6303):730–732. doi: 10.1038/348730a0. [DOI] [PubMed] [Google Scholar]
  2. Bigaud M., Pelton J. T. Discrimination between ETA- and ETB-receptor-mediated effects of endothelin-1 and [Ala1,3,11,15]endothelin-1 by BQ-123 in the anaesthetized rat. Br J Pharmacol. 1992 Dec;107(4):912–918. doi: 10.1111/j.1476-5381.1992.tb13385.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Emori T., Hirata Y., Marumo F. Specific receptors for endothelin-3 in cultured bovine endothelial cells and its cellular mechanism of action. FEBS Lett. 1990 Apr 24;263(2):261–264. doi: 10.1016/0014-5793(90)81388-5. [DOI] [PubMed] [Google Scholar]
  5. Fozard J. R., Part M. L. The role of nitric oxide in the regional vasodilator effects of endothelin-1 in the rat. Br J Pharmacol. 1992 Mar;105(3):744–750. doi: 10.1111/j.1476-5381.1992.tb09049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harrison V. J., Randriantsoa A., Schoeffter P. Heterogeneity of endothelin-sarafotoxin receptors mediating contraction of pig coronary artery. Br J Pharmacol. 1992 Mar;105(3):511–513. doi: 10.1111/j.1476-5381.1992.tb09009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hay D. W. Pharmacological evidence for distinct endothelin receptors in guinea-pig bronchus and aorta. Br J Pharmacol. 1992 Aug;106(4):759–761. doi: 10.1111/j.1476-5381.1992.tb14407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hermán F., Magyar K., Chabrier P. E., Braquet P., Filep J. Prostacyclin mediates antiaggregatory and hypotensive actions of endothelin in anaesthetized beagle dogs. Br J Pharmacol. 1989 Sep;98(1):38–40. doi: 10.1111/j.1476-5381.1989.tb16859.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ihara M., Fukuroda T., Saeki T., Nishikibe M., Kojiri K., Suda H., Yano M. An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis. Biochem Biophys Res Commun. 1991 Jul 15;178(1):132–137. doi: 10.1016/0006-291x(91)91789-f. [DOI] [PubMed] [Google Scholar]
  10. Lidbury P. S., Thiemermann C., Korbut R., Vane J. R. Endothelins release tissue plasminogen activator and prostanoids. Eur J Pharmacol. 1990 Sep 21;186(2-3):205–212. doi: 10.1016/0014-2999(90)90435-9. [DOI] [PubMed] [Google Scholar]
  11. McMurdo L., Corder R., Thiemermann C., Vane J. R. Incomplete inhibition of the pressor effects of endothelin-1 and related peptides in the anaesthetized rat with BQ-123 provides evidence for more than one vasoconstrictor receptor. Br J Pharmacol. 1993 Feb;108(2):557–561. doi: 10.1111/j.1476-5381.1993.tb12840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Samson W. K., Skala K. D., Alexander B. D., Huang F. L. Pituitary site of action of endothelin: selective inhibition of prolactin release in vitro. Biochem Biophys Res Commun. 1990 Jun 15;169(2):737–743. doi: 10.1016/0006-291x(90)90393-2. [DOI] [PubMed] [Google Scholar]
  14. Thiemermann C. Biosynthesis and interaction of endothelium-derived vasoactive mediators. Eicosanoids. 1991;4(4):187–202. [PubMed] [Google Scholar]
  15. Thiemermann C., Lidbury P. S., Thomas G. R., Vane J. R. Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S138–S142. [PubMed] [Google Scholar]
  16. Thiemermann C., Lidbury P., Thomas R., Vane J. Endothelin inhibits ex vivo platelet aggregation in the rabbit. Eur J Pharmacol. 1988 Dec 6;158(1-2):181–182. doi: 10.1016/0014-2999(88)90273-7. [DOI] [PubMed] [Google Scholar]
  17. Thiemermann C., May G. R., Page C. P., Vane J. R. Endothelin-1 inhibits platelet aggregation in vivo: a study with 111indium-labelled platelets. Br J Pharmacol. 1990 Feb;99(2):303–308. doi: 10.1111/j.1476-5381.1990.tb14699.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Warner T. D., Mitchell J. A., de Nucci G., Vane J. R. Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S85–S102. doi: 10.1097/00005344-198900135-00021. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Webb D. J. Endothelin receptors cloned, endothelin converting enzyme characterized and pathophysiological roles for endothelin proposed. Trends Pharmacol Sci. 1991 Feb;12(2):43–46. doi: 10.1016/0165-6147(91)90492-b. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Williams D. L., Jr, Jones K. L., Pettibone D. J., Lis E. V., Clineschmidt B. V. Sarafotoxin S6c: an agonist which distinguishes between endothelin receptor subtypes. Biochem Biophys Res Commun. 1991 Mar 15;175(2):556–561. doi: 10.1016/0006-291x(91)91601-8. [DOI] [PubMed] [Google Scholar]
  23. 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]
  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]

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