Endothelin-1-induced renal vasoconstriction is blunted by enalaprilat and enhanced by EDRF antagonist in awake normotensive rats

P. Madeddu, V. Anania, P. P. Parpaglia, C. Troffa, A. Pazzola, A. Soro, P. Manunta, G. Tonolo, M. P. Demontis, M. V. Varoni, M. G. Melis, N. Glorioso

Research output: Contribution to journalArticle

Abstract

We attempt to elucidate the putative indirect mechanisms by which endothelin-1 affects mean blood pressure and renal blood flow in normotensive awake rats. Endothelin-1 (700 pg/kg, i.v.) induced a short-lasting decrease followed by a prolonged increase in mean blood pressure (from 113 ± 4 to 92 ± 4 mmHg at 30 sec, 132 ± 7 mmHg at 10 min, and 129 ± 6 mmHg at 30 min, p <0.01), and caused a profound and long-lasting fall in renal blood flow as measured by Doppler flowmeter technique (from 2.87 ± 0.29 to 1.40 ± 0.37 kHz at 30 sec, 1.77 ± 0.32 kHz at 10 min and 2.10 ± 0.45 kHz at 30 min, p <0.01). Neither the receptor antagonist of bradykinin D-Arg0-Hyp3-Thi5,8-DPhe7-bradykinin (30 μg/kg/min, i.v.) nor the antagonist of angiotensin II Sar1,Thr8-angiotensin II (4 μg/kg/min, i.v.) altered the changes in mean blood pressure and renal blood flow induced by endothelin-1. The antagonist of EDRF synthesis, N(G)monomethyl-L-arginine (100 μg/kg/min, i.v.) enhanced the endothelin-1-induced increase in mean blood pressure (endothelin-1: 20 ± 2 mmHg vs endothelin-1 + EDRF antagonist: 39 ± 3 mmHg at 10 min, p <0.01) and decrease in renal blood flow (endothelin-1: -40 ± 4% vs endothelin-1 + EDRF antagonist: -73 ± 3% at 10 min, p <0.01). Enalaprilat (300 μg/kg, i.v.), an inhibitor of the enzyme which converts angiotensin I into angiotensin II and degrades kinins, overrode the systemic and renal hemodynamic effects of endothelin-1. We conclude that stimulation of EDRF release by endothelin-1 can buffer the systemic and renal hemodynamic effects of the latter compound. As the antagonist Sar1,Thr8-angiotensin did not prevent the action of endothelin-1, the mechanism by which enalaprilat protects against endothelin-1-induced vasoconstriction does not appear to be mediated by the blockade of angiotensin II formation.

Original languageEnglish
Pages (from-to)600-606
Number of pages7
JournalClinical and Investigative Medicine
Volume14
Issue number6
Publication statusPublished - 1991

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Keywords

  • angiotensin
  • converting enzyme inhibitors
  • endothelium
  • kinins
  • renal blood flow

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Madeddu, P., Anania, V., Parpaglia, P. P., Troffa, C., Pazzola, A., Soro, A., Manunta, P., Tonolo, G., Demontis, M. P., Varoni, M. V., Melis, M. G., & Glorioso, N. (1991). Endothelin-1-induced renal vasoconstriction is blunted by enalaprilat and enhanced by EDRF antagonist in awake normotensive rats. Clinical and Investigative Medicine, 14(6), 600-606.