Endothelin-1 produces pulmonary vasodilation in the intact newborn lamb

J. Wong, P. A. Vanderford, J. R. Fineman, R. Chang, S. J. Soifer

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60 Scopus citations

Abstract

The vascular endothelium mediates, in part, pulmonary vascular tone. Because endothelin-1 (ET-1), a paracrine hormone produced by vascular endothelial cells, has vasoactive properties, we investigated the hemodynamic effects of intrapulmonary injections of ET-1 in eight intact newborn lambs at rest and during pulmonary hypertension. At rest, ET-1 (50-1,000 ng/kg) did not change pulmonary arterial pressure. During pulmonary hypertension induced by the infusion of U46619 (a thromboxane A2 mimic), ET-1 (50-1,000 ng/kg) produced a selective dose-dependent decrease in pulmonary arterial pressure (5.8 ± 6.9 to 32.9 ± 6.9%; P < 0.05). Similarly, during pulmonary hypertension induced by alveolar hypoxia, ET-1 (50-500 ng/kg) produced a selective dose-dependent decrease in pulmonary arterial pressure (7.2 ± 3.6 to 26.1 ± 3.3%; P < 0.05). The decrease in pulmonary arterial pressure produced by ET-1 (250 ng/kg) was attenuated by N(ω)-nitro-L-arginine (an inhibitor of endothelium-derived nitric oxide synthesis, 23.7 ± 3.4 vs. 12.5 ± 4.7%; P < 0.05) and by glibenclamide (an ATP-gated potassium-channel blocker, 25.2 ± 5.0 vs. 9.6 ± 5.3%; P < 0.05) but not by meclofenamic acid (an inhibitor of prostaglandin synthesis). ET-1 is a pulmonary vasodilator during pulmonary hypertension in the intact newborn lamb. The vasodilating properties are mediated, in part, by release of endothelium-derived nitric oxide, and by activation of ATP-gated potassium channels.

Original languageEnglish (US)
Pages (from-to)H1318-H1325
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number4 34-4
DOIs
StatePublished - 1993

Keywords

  • endothelium-derived nitric oxide
  • potassium channels
  • pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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