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. 1994 Mar;111(3):729–732. doi: 10.1111/j.1476-5381.1994.tb14798.x

ETA receptor-mediated responses to endothelin-1 and big endothelin-1 in the rat kidney.

D M Pollock 1, T J Opgenorth 1
PMCID: PMC1910109  PMID: 8019752

Abstract

1. Renal clearance experiments were conducted in anaesthetized Sprague-Dawley rats to determine the effect of the ETA receptor antagonist, BQ-123, on the renal haemodynamic response to endothelin-1 (ET-1) and its precursor, big endothelin-1 (big ET-1) at doses that produce an equivalent degree of renal vasoconstriction. 2. Infusion of either big ET-1 at 100 pmol kg-1 min-1 or ET-1 at 12 pmol kg-1 min-1 for 60 min produced almost identical decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Big ET-1 produced an increase in mean arterial pressure (MAP) that was significantly larger than the increase produced by ET-1. 3. Co-infusion with BQ-123 (0.1 mg kg-1 min-1) prevented the rise in MAP produced by big ET-1 and completely blocked the renal response. Similarly, BQ-123 inhibited both the increase in MAP and the decrease in RPF and GFR produced by ET-1. 4. Big ET-1 but not ET-1, produced a significant increase in water and sodium excretion. BQ-123 had no effect on the diuretic and natriuretic response to big ET-1 consistent with possible ETB-mediated inhibition of tubular reabsorption. 5. We have previously shown that at higher doses of ET-1, BQ-123 was unable to inhibit the renal vasoconstrictor response despite blockade of the pressor response. Taken together, these results indicate that ET-1 activates primarily ETA receptors at moderately low doses to produce renal vasoconstriction while higher doses also involve non-ETA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Abassi Z. A., Tate J. E., Golomb E., Keiser H. R. Role of neutral endopeptidase in the metabolism of endothelin. Hypertension. 1992 Jul;20(1):89–95. doi: 10.1161/01.hyp.20.1.89. [DOI] [PubMed] [Google Scholar]
  2. Asaad M. M., Dorso C. R., Moreland S. M. Effects of neutral endopeptidase inhibition on the clearance of exogenously administered endothelin in Sprague-Dawley rats. J Cardiovasc Pharmacol. 1993 Apr;21(4):633–636. doi: 10.1097/00005344-199304000-00018. [DOI] [PubMed] [Google Scholar]
  3. Auguet M., Delaflotte S., Chabrier P. E., Braquet P. The vasoconstrictor action of big endothelin-1 is phosphoramidon-sensitive in rabbit saphenous artery, but not in saphenous vein. Eur J Pharmacol. 1992 Nov 24;224(1):101–102. doi: 10.1016/0014-2999(92)94827-i. [DOI] [PubMed] [Google Scholar]
  4. Benigni A., Zoja C., Corna D., Orisio S., Longaretti L., Bertani T., Remuzzi G. A specific endothelin subtype A receptor antagonist protects against injury in renal disease progression. Kidney Int. 1993 Aug;44(2):440–444. doi: 10.1038/ki.1993.263. [DOI] [PubMed] [Google Scholar]
  5. Cirino M., Motz C., Maw J., Ford-Hutchinson A. W., Yano M. BQ-153, a novel endothelin (ET)A antagonist, attenuates the renal vascular effects of endothelin-1. J Pharm Pharmacol. 1992 Sep;44(9):782–785. doi: 10.1111/j.2042-7158.1992.tb05522.x. [DOI] [PubMed] [Google Scholar]
  6. Clozel M., Gray G. A., Breu V., Löffler B. M., Osterwalder R. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun. 1992 Jul 31;186(2):867–873. doi: 10.1016/0006-291x(92)90826-7. [DOI] [PubMed] [Google Scholar]
  7. Cristol J. P., Warner T. D., Thiemermann C., Vane J. R. Mediation via different receptors of the vasoconstrictor effects of endothelins and sarafotoxins in the systemic circulation and renal vasculature of the anaesthetized rat. Br J Pharmacol. 1993 Mar;108(3):776–779. doi: 10.1111/j.1476-5381.1993.tb12877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hoffman A., Grossman E., Keiser H. R. Opposite effects of endothelin-1 and Big-endothelin-(1-39) on renal function in rats. Eur J Pharmacol. 1990 Jul 17;182(3):603–606. doi: 10.1016/0014-2999(90)90064-d. [DOI] [PubMed] [Google Scholar]
  9. Karet F. E., Kuc R. E., Davenport A. P. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int. 1993 Jul;44(1):36–42. doi: 10.1038/ki.1993.210. [DOI] [PubMed] [Google Scholar]
  10. Migas I., Bäcker A., Meyer-Lehnert H., Michel H., Wulfhekel U., Kramer H. J. Characteristics of endothelin receptors and intracellular signalling in porcine inner medullary collecting duct cells. Am J Hypertens. 1993 Jul;6(7 Pt 1):611–618. doi: 10.1093/ajh/6.7.611. [DOI] [PubMed] [Google Scholar]
  11. Mino N., Kobayashi M., Nakajima A., Amano H., Shimamoto K., Ishikawa K., Watanabe K., Nishikibe M., Yano M., Ikemoto F. Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats. Eur J Pharmacol. 1992 Oct 6;221(1):77–83. doi: 10.1016/0014-2999(92)90774-x. [DOI] [PubMed] [Google Scholar]
  12. Nambi P., Wu H. L., Pullen M., Aiyar N., Bryan H., Elliott J. Identification of endothelin receptor subtypes in rat kidney cortex using subtype-selective ligands. Mol Pharmacol. 1992 Aug;42(2):336–339. [PubMed] [Google Scholar]
  13. Oishi R., Nonoguchi H., Tomita K., Marumo F. Endothelin-1 inhibits AVP-stimulated osmotic water permeability in rat inner medullary collecting duct. Am J Physiol. 1991 Dec;261(6 Pt 2):F951–F956. doi: 10.1152/ajprenal.1991.261.6.F951. [DOI] [PubMed] [Google Scholar]
  14. Opgenorth T. J., Wu-Wong J. R., Shiosaki K. Endothelin-converting enzymes. FASEB J. 1992 Jun;6(9):2653–2659. doi: 10.1096/fasebj.6.9.1612289. [DOI] [PubMed] [Google Scholar]
  15. Pollock D. M., Opgenorth T. J. Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation. Am J Physiol. 1993 Jan;264(1 Pt 2):R222–R226. doi: 10.1152/ajpregu.1993.264.1.R222. [DOI] [PubMed] [Google Scholar]
  16. Pollock D. M., Opgenorth T. J. Evidence for metalloprotease involvement in the in vivo effects of big endothelin 1. Am J Physiol. 1991 Jul;261(1 Pt 2):R257–R263. doi: 10.1152/ajpregu.1991.261.1.R257. [DOI] [PubMed] [Google Scholar]
  17. Salvati P., Dho L., Calabresi M., Rosa B., Patrono C. Evidence for a direct vasoconstrictor effect of big endothelin-1 in the rat kidney. Eur J Pharmacol. 1992 Oct 20;221(2-3):267–273. doi: 10.1016/0014-2999(92)90712-d. [DOI] [PubMed] [Google Scholar]
  18. Terada Y., Tomita K., Nonoguchi H., Marumo F. Different localization of two types of endothelin receptor mRNA in microdissected rat nephron segments using reverse transcription and polymerase chain reaction assay. J Clin Invest. 1992 Jul;90(1):107–112. doi: 10.1172/JCI115822. [DOI] [PMC free article] [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. 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]
  21. Zeidel M. L., Brady H. R., Kone B. C., Gullans S. R., Brenner B. M. Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells. Am J Physiol. 1989 Dec;257(6 Pt 1):C1101–C1107. doi: 10.1152/ajpcell.1989.257.6.C1101. [DOI] [PubMed] [Google Scholar]

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