Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1991 Feb;433:25–39. doi: 10.1113/jphysiol.1991.sp018412

Haemodynamic and renal tubular effects of low doses of endothelin in anaesthetized rats.

P J Harris 1, J Zhuo 1, F A Mendelsohn 1, S L Skinner 1
PMCID: PMC1181357  PMID: 1841941

Abstract

1. Renal haemodynamic and tubular transport responses to low-dose infusions (1 and 10 ng kg-1 min-1) of endothelin were investigated in anaesthetized rats. 2. Both doses caused transient increases in mean arterial blood pressure (17 +/- 5 mmHg, P < 0.05 at 1 ng kg-1 min-1) followed by sustained hypotension (-14 +/- 5 mmHg, P < 0.05), reduced renal vascular resistance (-42%, P < 0.05) and increased renal plasma flow (46%, P < 0.05). Glomerular filtration rate was unchanged. 3. Each dose caused profound diuresis and natriuresis. At 1 ng kg-1 min-1 urine flow rate and fractional water excretion increased 5-fold and fractional sodium excretion 10-fold. Fractional potassium excretion and solute-free water clearance were unaltered. 4. End-proximal fluid delivery estimated by lithium clearance doubled (P < 0.05) and fractional proximal and distal sodium reabsorption decreased 10-20% (P < 0.05). Absolute proximal reabsorption also fell with the higher dose. 5. Hypotension and natriuresis persisted for 30 min after terminating infusions. Time-control animals showed no changes in haemodynamics or renal tubular transport. 6. It is concluded that endothelin, at low concentrations, causes renal vasodilatation with concomitant natriuresis due to reduced sodium transport in proximal and distal nephron segments.

Full text

PDF
34

Selected References

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

  1. Chai S. Y., Sexton P. M., Allen A. M., Figdor R., Mendelsohn F. A. In vitro autoradiographic localization of ANP receptors in rat kidney and adrenal gland. Am J Physiol. 1986 Apr;250(4 Pt 2):F753–F757. doi: 10.1152/ajprenal.1986.250.4.F753. [DOI] [PubMed] [Google Scholar]
  2. Cocks T. M., Broughton A., Dib M., Sudhir K., Angus J. A. Endothelin is blood vessel selective: studies on a variety of human and dog vessels in vitro and on regional blood flow in the conscious rabbit. Clin Exp Pharmacol Physiol. 1989 Apr;16(4):243–246. doi: 10.1111/j.1440-1681.1989.tb01551.x. [DOI] [PubMed] [Google Scholar]
  3. FUHR J., KACZMARCZYK J., KRUTTGEN C. D. Eine einfache colorimetrische Methode zur Inulinbestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin Wochenschr. 1955 Aug 1;33(29-30):729–730. doi: 10.1007/BF01473295. [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. Fukuda Y., Hirata Y., Yoshimi H., Kojima T., Kobayashi Y., Yanagisawa M., Masaki T. Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes. Biochem Biophys Res Commun. 1988 Aug 30;155(1):167–172. doi: 10.1016/s0006-291x(88)81064-7. [DOI] [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. Harris P. J., Skinner S. L., Zhuo J. Haemodynamic and renal tubular responses to low-dose infusion or bolus injection of the peptide ANF in anaesthetized rats. J Physiol. 1989 May;412:309–320. doi: 10.1113/jphysiol.1989.sp017617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harris P. J., Zhuo J. L., Skinner S. L. Effects of angiotensins II and III on glomerulotubular balance in rats. Clin Exp Pharmacol Physiol. 1987 Jun;14(6):489–502. doi: 10.1111/j.1440-1681.1987.tb01505.x. [DOI] [PubMed] [Google Scholar]
  9. Hirata Y., Matsuoka H., Kimura K., Fukui K., Hayakawa H., Suzuki E., Sugimoto T., Sugimoto T., Yanagisawa M., Masaki T. Renal vasoconstriction by the endothelial cell-derived peptide endothelin in spontaneously hypertensive rats. Circ Res. 1989 Nov;65(5):1370–1379. doi: 10.1161/01.res.65.5.1370. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kirchner K. A. Lithium as a marker for proximal tubular delivery during low salt intake and diuretic infusion. Am J Physiol. 1987 Jul;253(1 Pt 2):F188–F196. doi: 10.1152/ajprenal.1987.253.1.F188. [DOI] [PubMed] [Google Scholar]
  12. Kohzuki M., Johnston C. I., Chai S. Y., Casley D. J., Mendelsohn F. A. Localization of endothelin receptors in rat kidney. Eur J Pharmacol. 1989 Jan 24;160(1):193–194. doi: 10.1016/0014-2999(89)90673-0. [DOI] [PubMed] [Google Scholar]
  13. Lippton H., Goff J., Hyman A. Effects of endothelin in the systemic and renal vascular beds in vivo. Eur J Pharmacol. 1988 Oct 11;155(1-2):197–199. doi: 10.1016/0014-2999(88)90424-4. [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. Mendelsohn F. A., Dunbar M., Allen A., Chou S. T., Millan M. A., Aguilera G., Catt K. J. Angiotensin II receptors in the kidney. Fed Proc. 1986 Apr;45(5):1420–1425. [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. Minkes R. K., Kadowitz P. J. Influence of endothelin on systemic arterial pressure and regional blood flow in the cat. Eur J Pharmacol. 1989 Apr 12;163(1):163–166. doi: 10.1016/0014-2999(89)90412-3. [DOI] [PubMed] [Google Scholar]
  18. Minkes R. K., MacMillan L. A., Bellan J. A., Kerstein M. D., McNamara D. B., Kadowitz P. J. Analysis of regional responses to endothelin in hindquarters vascular bed of cats. Am J Physiol. 1989 Feb;256(2 Pt 2):H598–H602. doi: 10.1152/ajpheart.1989.256.2.H598. [DOI] [PubMed] [Google Scholar]
  19. Orita Y., Fujiwara Y., Ochi S., Takama T., Fukunaga M., Yokoyama K. Endothelin-1 receptors in rat renal glomeruli. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S159–S161. doi: 10.1097/00005344-198900135-00043. [DOI] [PubMed] [Google Scholar]
  20. Rakugi H., Nakamaru M., Saito H., Higaki J., Ogihara T. Endothelin inhibits renin release from isolated rat glomeruli. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1244–1247. doi: 10.1016/s0006-291x(88)81273-7. [DOI] [PubMed] [Google Scholar]
  21. Scoggins B. A., Spence C. D., Parkes D. G., McDonald M., Wade J. D., Coghlan J. P. Cardiovascular actions of human endothelin in conscious sheep. Clin Exp Pharmacol Physiol. 1989 Apr;16(4):235–238. doi: 10.1111/j.1440-1681.1989.tb01549.x. [DOI] [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. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Suzuki N., Matsumoto H., Kitada C., Yanagisawa M., Miyauchi T., Masaki T., Fujino M. Immunoreactive endothelin-1 in plasma detected by a sandwich-type enzyme immunoassay. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S151–S152. doi: 10.1097/00005344-198900135-00039. [DOI] [PubMed] [Google Scholar]
  25. Thomsen K., Leyssac P. P. Effect of dietary sodium content on renal handling of lithium. Experiments in conscious diabetes insipidus rats. Pflugers Arch. 1986 Jul;407(1):55–58. doi: 10.1007/BF00580720. [DOI] [PubMed] [Google Scholar]
  26. Thomsen K. Lithium clearance: a new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron. 1984;37(4):217–223. doi: 10.1159/000183252. [DOI] [PubMed] [Google Scholar]
  27. Tomobe Y., Miyauchi T., Saito A., Yanagisawa M., Kimura S., Goto K., Masaki T. Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol. 1988 Aug 2;152(3):373–374. doi: 10.1016/0014-2999(88)90736-4. [DOI] [PubMed] [Google Scholar]
  28. Tsunoda K., Hodsman G. P., Sumithran E., Johnston C. I. Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction. Circ Res. 1986 Sep;59(3):256–261. doi: 10.1161/01.res.59.3.256. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Winquist R. J., Bunting P. B., Garsky V. M., Lumma P. K., Schofield T. L. Prominent depressor response to endothelin in spontaneously hypertensive rats. Eur J Pharmacol. 1989 Apr 12;163(1):199–203. doi: 10.1016/0014-2999(89)90420-2. [DOI] [PubMed] [Google Scholar]
  31. Winquist R. J., Scott A. L., Vlasuk G. P. Enhanced release of atrial natriuretic factor by endothelin in atria from hypertensive rats. Hypertension. 1989 Jul;14(1):111–114. doi: 10.1161/01.hyp.14.1.111. [DOI] [PubMed] [Google Scholar]
  32. Wright C. E., Fozard J. R. Regional vasodilation is a prominent feature of the haemodynamic response to endothelin in anaesthetized, spontaneously hypertensive rats. Eur J Pharmacol. 1988 Oct 11;155(1-2):201–203. doi: 10.1016/0014-2999(88)90425-6. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Zhuo J. L., Harris P. J., Skinner S. L. Atrial natriuretic factor modulates proximal glomerulotubular balance in anesthetized rats. Hypertension. 1989 Dec;14(6):666–673. doi: 10.1161/01.hyp.14.6.666. [DOI] [PubMed] [Google Scholar]
  35. 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 The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES