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. 1993 Mar;108(3):838–843. doi: 10.1111/j.1476-5381.1993.tb12887.x

Endothelin-1 in the rabbit: interactions with cyclo-oxygenase and NO-synthase products.

M E Rogerson 1, H S Cairns 1, L D Fairbanks 1, J Westwick 1, G H Neild 1
PMCID: PMC1908050  PMID: 7682141

Abstract

1. Endothelin-1 infusion (5-40 pmol kg-1 min-1) in the normal anaesthetized rabbit, produced a dose-dependent increase in mean arterial blood pressure (MAP) and reduced renal blood flow (RBF) and glomerular filtration rate (GFR), when compared with an equivalent infusion of physiological saline. 2. Endothelin, 20 pmol kg-1 min-1, was also assessed in animals pretreated with either indomethacin (2 mg kg-1), methylene blue (1.6 mg kg-1 h-1) or NG-monomethyl L-arginine (L-NMMA, 10 mg kg-1 h-1). 3. The effect of endothelin on MAP and RBF was enhanced (P = 0.05 and < 0.01 respectively) by the cyclo-oxygenase inhibitor, indomethacin, without any significant change in the effect on GFR. 4. Methylene blue and L-NMMA, inhibitors of endothelium-derived relaxant factor (EDRF), enhanced the effect of endothelin on each of the parameters measured (P < 0.01). 5. Our results are consistent with endothelin having a predominant effect on pre-glomerular vascular resistance to reduce GFR. Endothelin appears to stimulate the release of vasodilator prostanoids and EDRF which oppose its effects. Thus endothelin may have an important role in the complex control of GFR in the rabbit.

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Selected References

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  1. Badr K. F., Murray J. J., Breyer M. D., Takahashi K., Inagami T., Harris R. C. Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Elucidation of signal transduction pathways. J Clin Invest. 1989 Jan;83(1):336–342. doi: 10.1172/JCI113880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cairns H. S., Rogerson M. E., Fairbanks L. D., Neild G. H., Westwick J. Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney. Br J Pharmacol. 1989 Sep;98(1):155–160. doi: 10.1111/j.1476-5381.1989.tb16876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Firth J. D., Ratcliffe P. J., Raine A. E., Ledingham J. G. Endothelin: an important factor in acute renal failure? Lancet. 1988 Nov 19;2(8621):1179–1182. doi: 10.1016/s0140-6736(88)90243-7. [DOI] [PubMed] [Google Scholar]
  5. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  6. 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]
  7. Ignarro L. J., Buga G. M., Wood K. S., Byrns R. E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265–9269. doi: 10.1073/pnas.84.24.9265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ignarro L. J., Harbison R. G., Wood K. S., Kadowitz P. J. Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: stimulation by acetylcholine, bradykinin and arachidonic acid. J Pharmacol Exp Ther. 1986 Jun;237(3):893–900. [PubMed] [Google Scholar]
  9. Kastner P. R., Hall J. E., Guyton A. C. Control of glomerular filtration rate: role of intrarenally formed angiotensin II. Am J Physiol. 1984 Jun;246(6 Pt 2):F897–F906. doi: 10.1152/ajprenal.1984.246.6.F897. [DOI] [PubMed] [Google Scholar]
  10. Kon V., Sugiura M., Inagami T., Harvie B. R., Ichikawa I., Hoover R. L. Role of endothelin in cyclosporine-induced glomerular dysfunction. Kidney Int. 1990 Jun;37(6):1487–1491. doi: 10.1038/ki.1990.139. [DOI] [PubMed] [Google Scholar]
  11. Kon V., Yoshioka T., Fogo A., Ichikawa I. Glomerular actions of endothelin in vivo. J Clin Invest. 1989 May;83(5):1762–1767. doi: 10.1172/JCI114079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koseki C., Imai M., Hirata Y., Yanagisawa M., Masaki T. Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide? Am J Physiol. 1989 Apr;256(4 Pt 2):R858–R866. doi: 10.1152/ajpregu.1989.256.4.R858. [DOI] [PubMed] [Google Scholar]
  13. Loutzenhiser R., Epstein M., Hayashi K., Horton C. Direct visualization of effects of endothelin on the renal microvasculature. Am J Physiol. 1990 Jan;258(1 Pt 2):F61–F68. doi: 10.1152/ajprenal.1990.258.1.F61. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Matsumura Y., Hisaki K., Ohyama T., Hayashi K., Morimoto S. Effects of endothelin on renal function and renin secretion in anesthetized rats. Eur J Pharmacol. 1989 Aug 3;166(3):577–580. doi: 10.1016/0014-2999(89)90380-4. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Palmer R. M., Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):348–352. doi: 10.1016/s0006-291x(89)80219-0. [DOI] [PubMed] [Google Scholar]
  18. Rees D. D., Palmer R. M., Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989 May;86(9):3375–3378. doi: 10.1073/pnas.86.9.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Resink T. J., Scott-Burden T., Bühler F. R. Activation of phospholipase A2 by endothelin in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):279–286. doi: 10.1016/s0006-291x(89)80209-8. [DOI] [PubMed] [Google Scholar]
  20. Rogerson M. E., Cairns H. S., Fairbanks L. D., Neild G. H., Westwick J. Endothelin in the anaesthetised rabbit: action and interaction in the renal microcirculation. Br J Pharmacol. 1989 Dec;98 (Suppl):841P–841P. [PubMed] [Google Scholar]
  21. Rubanyi G. M., Vanhoutte P. M. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol. 1985 Jul;364:45–56. doi: 10.1113/jphysiol.1985.sp015728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simonson M. S., Wann S., Mené P., Dubyak G. R., Kester M., Nakazato Y., Sedor J. R., Dunn M. J. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest. 1989 Feb;83(2):708–712. doi: 10.1172/JCI113935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takagi M., Matsuoka H., Atarashi K., Yagi S. Endothelin: a new inhibitor of renin release. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1164–1168. doi: 10.1016/s0006-291x(88)80996-3. [DOI] [PubMed] [Google Scholar]
  24. Terragno N. A., Terragno A., Early J. A., Roberts M. A., McGiff J. C. Endogenous prostaglandin synthesis inhibitor in the renal cortex. Effects on production of prostacyclin by renal blood vessels. Clin Sci Mol Med Suppl. 1978 Dec;4:199s–202s. doi: 10.1042/cs055199s. [DOI] [PubMed] [Google Scholar]
  25. Tolins J. P., Palmer R. M., Moncada S., Raij L. Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol. 1990 Mar;258(3 Pt 2):H655–H662. doi: 10.1152/ajpheart.1990.258.3.H655. [DOI] [PubMed] [Google Scholar]
  26. Vanhoutte P. M. The endothelium--modulator of vascular smooth-muscle tone. N Engl J Med. 1988 Aug 25;319(8):512–513. doi: 10.1056/NEJM198808253190809. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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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