The effect of the endothelin ET(A) receptor antagonist CI-1020 on hypoxic pulmonary vasoconstriction

Eur J Pharmacol. 1999 Jun 25;374(3):367-75. doi: 10.1016/s0014-2999(99)00300-3.


The mechanism of Hypoxic Pulmonary Vasoconstriction is unknown. The role of endothelin-1 in hypoxic pulmonary vasoconstriction was studied in precontracted small and large pulmonary arteries using the endothelin ETA receptor antagonist sodium-2-benzol [1,3]dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxy-ben zyl)-but-2-enoate (CI-1020). Small rat pulmonary arteries exhibit a mixed endothelin ETA receptor and endothelin ETB2 receptor population whereas large rat pulmonary arteries contain only endothelin ETA receptors. CI-1020 inhibited endothelin-1 in small vessels via endothelin ETA receptor blockade (1 and 10 microM) and at high concentrations via endothelin ETA receptor and endothelin ETB2 receptor blockade (100 microM). CI-1020 (0.01, 0.1 and 1 microM) inhibited endothelin-1 in large vessels via endothelin ETA receptor blockade alone. CI-1020 (1, 10 and 100 microM) significantly reduced hypoxic pulmonary vasoconstriction in small vessels, by -9.8+/-1.4, -9.2+/-2.3 and -8.0+/-1.7% 80 mM K+, respectively, compared to +2.5+/-4.2% with vehicle (P < 0.05). CI-1020 (0.01, 0.1 and 1 microM) had no significant effect upon hypoxic pulmonary vasoconstriction in large vessels. In small, but not large, pulmonary arteries hypoxic pulmonary vasoconstriction is due in part to the action of endothelin-1 at the endothelin ETA receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dioxoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / pharmacology
  • Hypoxia / physiopathology*
  • In Vitro Techniques
  • Male
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiopathology
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology


  • Dioxoles
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • PD 156707
  • Receptor, Endothelin A