Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat.

Academic Article

Abstract

  • Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin-1 (ET-1) levels and with selective enhancement in ET-1 peptide and mRNA and endothelin-A (ETA) receptor mRNA levels in rat lung. The current study tested the hypothesis that endogenous ET-1 can account for hypoxia-induced pulmonary hypertension via a paracrine effect on ETA receptors in lung. Intravenous infusion of the ETA receptor antagonist BQ-123 (D-Trp-D-Asp-Pro-D-Val-Leu) (0.4 mg/microliters at 1 microliter/h) into Sprague-Dawley rats beginning 4 h before and for 90 min during normobaric hypoxia (10% O2) markedly attenuated the hypoxic response: mean pulmonary artery pressure increased from 17.2 +/- 0.7 to 29.0 +/- 1.2 mmHg in saline control rats but did not increase from baseline in BQ-123-treated rats. BQ-123 did not alter systemic arterial pressure, heart rate, or plasma endothelin-1 levels. These findings suggest that ET-1 synthesized in lung in response to hypoxia acts locally on ETA receptors to cause pulmonary hypertension.
  • Authors

    Published In

    Keywords

  • Acute Disease, Animals, Blood Pressure, Endothelin Receptor Antagonists, Heart Rate, Hypertension, Pulmonary, Hypoxia, Male, Peptides, Cyclic, Pulmonary Artery, Rats, Rats, Sprague-Dawley, Receptor, Endothelin A
  • Digital Object Identifier (doi)

    Author List

  • Oparil S; Chen SJ; Meng QC; Elton TS; Yano M; Chen YF
  • Start Page

  • L95
  • End Page

  • 100
  • Volume

  • 268
  • Issue

  • 1 Pt 1