Mechanism of hypoxic pulmonary vasoconstriction involves ET(A) receptor-mediated inhibition of K(ATP) channel

Am J Physiol Lung Cell Mol Physiol. 2000 Mar;278(3):L434-42. doi: 10.1152/ajplung.2000.278.3.L434.


There is controversy on the role of endothelin (ET)-1 in the mechanism of hypoxic pulmonary vasoconstriction (HPV). Although HPV is inhibited by ET-1 subtype A (ET(A))-receptor antagonists in animals, it has been reported that ET(A)-receptor blockade does not affect HPV in isolated lungs. Thus we reassessed the role of ET-1 in HPV in both rats and isolated blood- and physiological salt solution (PSS)-perfused rat lungs. In rats, the ET(A)-receptor antagonist BQ-123 and the nonselective ET(A)- and ET(B)-receptor antagonist PD-145065, but not the ET(B)-receptor antagonist BQ-788, inhibited HPV. Similarly, BQ-123, but not BQ-788, attenuated HPV in blood-perfused lungs. In PSS-perfused lungs, either BQ-123, BQ-788, or the combination of both attenuated HPV equally. Inhibition of HPV by combined BQ-123 and BQ-788 in PSS-perfused lungs was prevented by costimulation with angiotensin II. The ATP-sensitive K(+) (K(ATP))-channel blocker glibenclamide also prevented inhibition of HPV by BQ-123 in both lungs and rats. These results suggest that ET-1 contributes to HPV in both isolated lungs and intact animals through ET(A) receptor-mediated suppression of K(ATP)-channel activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / physiology*
  • Animals
  • Blood
  • Endothelin Receptor Antagonists
  • Glyburide / pharmacology
  • Hypoxia / physiopathology*
  • In Vitro Techniques
  • Male
  • Peptides, Cyclic / pharmacology
  • Perfusion
  • Potassium Channel Blockers*
  • Pulmonary Circulation / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A
  • Receptors, Endothelin / physiology*
  • Sodium Chloride
  • Vasoconstriction* / drug effects


  • Endothelin Receptor Antagonists
  • Peptides, Cyclic
  • Potassium Channel Blockers
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • Sodium Chloride
  • Adenosine Triphosphate
  • cyclo(Trp-Asp-Pro-Val-Leu)
  • Glyburide