Endothelin-B-receptor-selective antagonist inhibits endothelin-1 induced potentiation on the vasoconstriction to noradrenaline and angiotensin II

Mario Gössl, Anna Mitchell, Amir Lerman, Anabelle Opazo Saez, Rafael F. Schäfers, Raimund Erbel, Thomas Philipp, René R. Wenzel

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objective: Endothelin-A-receptor-antagonists inhibit angiotensin II- and noradrenaline-induced vasoconstriction. Whether functional constrictive endothelin-B-receptors play a role in the endothelin-1-mediated potentiation of vasoconstriction to angiotensin II and noradrenaline is thus far unknown. Methods: We studied the effects of noradrenaline and angiotensin II (10 -14,-16,-18 mol/l) in the presence of exogenous endothelin-1 (10 -18 mol/l) with and without selective endothelin-B-receptor-blockade by BQ-788 (10-8 mol/l) and dual receptor blockade with BQ-788 and the endothelin-A-selective antagonist BQ-123 (10-8 mol/l) in 14 healthy male volunteers (aged 20-28). Studies were performed in the human skin microcirculation under in vivo conditions using laser-Doppler flowmetry and double injection technique. The area under the time-response curve of all doses was calculated. Results: Endothelin-1 potentiated the effects of angiotensin II and noradrenaline (-944 ± 139 perfusion units (PU), P < 0.01; -926 ± 117 PU, P < 0.05, respectively). In the presence of BQ-788, the potentiating effect of endothelin-1 was significantly blunted (-624 ± 132 PU, P < 0.01; -549 ± 136 PU, P < 0.01, respectively). In the presence of BQ-123 and BQ-788 the vasoconstriction was fully inhibited (431 ± 108 PU, P < 0.001 and 421 ± 86 PU, P < 0.001, respectively). Conclusions: These data suggest that functional vasoconstrictive endothelin-B receptors on vascular smooth muscle cells may contribute to the potentiating effects of high local concentrations of endothelin-1 on the vasoconstriction to noradrenaline and angiotensin II in human microcirculation.

Original languageEnglish (US)
Pages (from-to)1909-1916
Number of pages8
JournalJournal of hypertension
Volume22
Issue number10
DOIs
StatePublished - Oct 2004

Keywords

  • Angiotensin II
  • BQ-788 and BQ-123
  • Endothelin-1
  • Microcirculation
  • Noradrenaline
  • Potentiation
  • Vasoconstriction

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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