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. 1993 Jul;109(3):880–886. doi: 10.1111/j.1476-5381.1993.tb13657.x

Enhancement by endothelin-1 of microvascular permeability via the activation of ETA receptors.

J G Filep 1, M G Sirois 1, E Földes-Filep 1, A Rousseau 1, G E Plante 1, A Fournier 1, M Yano 1, P Sirois 1
PMCID: PMC2175619  PMID: 8358577

Abstract

1. The objective of the present experiments was to assess the involvement of endothelin-A (ETA) receptors in mediating the effects of endothelin-1 on microvascular permeability in conscious rats. 2. Bolus injection of endothelin-1 (0.1 and 1 nmol kg-1, i.v.) resulted in a dose-dependent prolonged pressor effect preceded by a transient depressor response. These changes were accompanied by a dose-dependent loss of plasma volume. Endothelin-1 (1 nmol kg-1) enhanced the vascular permeability of the upper and lower bronchi, kidney, stomach, duodenum and spleen (up to 270%) as measured by the extravasation of Evans blue dye. 3. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.) significantly blunted the pressor response to endothelin-1 without affecting the depressor response. BQ-123 inhibited by 87% the endothelin-1 (1 nmol kg-1)-induced plasma volume loss. BQ-123 markedly attenuated protein extravasation elicited by endothelin-1 in the upper and lower bronchi and kidney, whereas it completely inhibited the permeability effect of endothelin-1 in the stomach and duodenum. BQ-123 by itself had no significant effect on the parameters studied. 4. The endothelin-1 analogue, [Trp(For)21]-endothelin-1, in which Trp21 is formylated, was as potent a pressor agent as endothelin-1, but had no depressor action. Bolus injection of [Trp(For)21]-endothelin-1 (0.1 and 1 nmol kg-1, i.v.) evoked similar plasma volume losses to those observed following administration of equimolar doses of endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Amelang E., Prasad C. M., Raymond R. M., Grega G. J. Interactions among inflammatory mediators on edema formation in the canine forelimb. Circ Res. 1981 Aug;49(2):298–306. doi: 10.1161/01.res.49.2.298. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Brain S. D., Crossman D. C., Buckley T. L., Williams T. J. Endothelin-1: demonstration of potent effects on the microcirculation of humans and other species. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S147–S150. [PubMed] [Google Scholar]
  4. Brain S. D., Tippins J. R., Williams T. J. Endothelin induces potent microvascular constriction. Br J Pharmacol. 1988 Dec;95(4):1005–1007. doi: 10.1111/j.1476-5381.1988.tb11731.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chander C. L., Moore A. R., Desa F. M., Howat D. W., Willoughby D. A. Anti-inflammatory effects of endothelin-1. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S218–S219. doi: 10.1097/00005344-198900135-00064. [DOI] [PubMed] [Google Scholar]
  6. Dahlöf B., Gustafsson D., Hedner T., Jern S., Hansson L. Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reaction. J Hypertens. 1990 Sep;8(9):811–817. doi: 10.1097/00004872-199009000-00004. [DOI] [PubMed] [Google Scholar]
  7. Douglas S. A., Hiley C. R. Endothelium-dependent mesenteric vasorelaxant effects and systemic actions of endothelin (16-21) and other endothelin-related peptides in the rat. Br J Pharmacol. 1991 Oct;104(2):311–320. doi: 10.1111/j.1476-5381.1991.tb12428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Filep J. G., Földes-Filep E., Rousseau A., Fournier A., Sirois P., Yano M. Endothelin-1 enhances vascular permeability in the rat heart through the ETA receptor. Eur J Pharmacol. 1992 Aug 25;219(2):343–344. doi: 10.1016/0014-2999(92)90318-x. [DOI] [PubMed] [Google Scholar]
  9. Filep J. G., Rousseau A., Fournier A., Sirois P. Structure-activity relationship of analogues of endothelin-1: dissociation of hypotensive and pressor actions. Eur J Pharmacol. 1992 Sep 22;220(2-3):263–266. doi: 10.1016/0014-2999(92)90757-u. [DOI] [PubMed] [Google Scholar]
  10. Filep J. G., Sirois M. G., Rousseau A., Fournier A., Sirois P. Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor. Br J Pharmacol. 1991 Dec;104(4):797–804. doi: 10.1111/j.1476-5381.1991.tb12509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Filep J., Földes-Filep E., Frölich J. C. Vascular responses to leukotriene B4, C4 and D4 following FPL 55712, indomethacin, saralasin, phentolamine and verapamil in the conscious rat. Br J Pharmacol. 1987 Feb;90(2):431–439. doi: 10.1111/j.1476-5381.1987.tb08973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goetz K. L., Wang B. C., Madwed J. B., Zhu J. L., Leadley R. J., Jr Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol. 1988 Dec;255(6 Pt 2):R1064–R1068. doi: 10.1152/ajpregu.1988.255.6.R1064. [DOI] [PubMed] [Google Scholar]
  13. Grega G. J., Adamski S. W., Dobbins D. E. Physiological and pharmacological evidence for the regulation of permeability. Fed Proc. 1986 Feb;45(2):96–100. [PubMed] [Google Scholar]
  14. 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]
  15. Henriques M. G., Rae G. A., Cordeiro R. S., Williams T. J. Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse. Br J Pharmacol. 1992 Jul;106(3):579–582. doi: 10.1111/j.1476-5381.1992.tb14378.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. López-Farré A., Montañs I., Millás I., López-Novoa J. M. Effect of endothelin on renal function in rats. Eur J Pharmacol. 1989 Apr 12;163(1):187–189. doi: 10.1016/0014-2999(89)90417-2. [DOI] [PubMed] [Google Scholar]
  19. Miller W. L., Redfield M. M., Burnett J. C., Jr Integrated cardiac, renal, and endocrine actions of endothelin. J Clin Invest. 1989 Jan;83(1):317–320. doi: 10.1172/JCI113876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saeki T., Ihara M., Fukuroda T., Yamagiwa M., Yano M. [Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity. Biochem Biophys Res Commun. 1991 Aug 30;179(1):286–292. doi: 10.1016/0006-291x(91)91367-l. [DOI] [PubMed] [Google Scholar]
  21. Sakurai T., Yanagisawa M., Masaki T. Molecular characterization of endothelin receptors. Trends Pharmacol Sci. 1992 Mar;13(3):103–108. doi: 10.1016/0165-6147(92)90038-8. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Shirakami G., Nakao K., Saito Y., Magaribuchi T., Jougasaki M., Mukoyama M., Arai H., Hosoda K., Suga S., Ogawa Y. Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats. Life Sci. 1991;48(10):969–976. doi: 10.1016/0024-3205(91)90362-f. [DOI] [PubMed] [Google Scholar]
  24. Sirois M. G., Filep J. G., Rousseau A., Fournier A., Plante G. E., Sirois P. Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2. Eur J Pharmacol. 1992 Apr 22;214(2-3):119–125. doi: 10.1016/0014-2999(92)90108-g. [DOI] [PubMed] [Google Scholar]
  25. Sokolovsky M. Structure-function relationships of endothelins, sarafotoxins, and their receptor subtypes. J Neurochem. 1992 Sep;59(3):809–821. doi: 10.1111/j.1471-4159.1992.tb08318.x. [DOI] [PubMed] [Google Scholar]
  26. Valentin J. P., Gardner D. G., Wiedemann E., Humphreys M. H. Modulation of endothelin effects on blood pressure and hematocrit by atrial natriuretic peptide. Hypertension. 1991 Jun;17(6 Pt 2):864–869. doi: 10.1161/01.hyp.17.6.864. [DOI] [PubMed] [Google Scholar]
  27. Warner T. D. Simultaneous perfusion of rat isolated superior mesenteric arterial and venous beds: comparison of their vasoconstrictor and vasodilator responses to agonists. Br J Pharmacol. 1990 Feb;99(2):427–433. doi: 10.1111/j.1476-5381.1990.tb14720.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yang Z. H., Bühler F. R., Diederich D., Lüscher T. F. Different effects of endothelin-1 on cAMP- and cGMP-mediated vascular relaxation in human arteries and veins: comparison with norepinephrine. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S129–S142. doi: 10.1097/00005344-198900135-00032. [DOI] [PubMed] [Google Scholar]
  29. Zimmerman R. S., Martinez A. J., Maymind M., Barbee R. W. Effect of endothelin on plasma volume and albumin escape. Circ Res. 1992 May;70(5):1027–1034. doi: 10.1161/01.res.70.5.1027. [DOI] [PubMed] [Google Scholar]

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