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Redox activation of intracellular calcium release channels (ryanodine receptors) in the sustained phase of hypoxia-induced pulmonary vasoconstriction.

Publication ,  Journal Article
Du, W; Frazier, M; McMahon, TJ; Eu, JP
Published in: Chest
December 2005

Hypoxia-induced pulmonary vasoconstriction (HPV) is an important adaptive process that remains incompletely understood. In preconstricted rat pulmonary arteries (inner diameter, 250 to 400 microm), hypoxia (pO2 approximately 10 mm Hg) induces an initial transient phase and a more slowly developing sustained phase of vasoconstriction. Since the release of calcium ions (Ca2+) from intracellular stores by redox-sensitive intracellular Ca2+ release channels known as ryanodine receptors (RyRs) in pulmonary arterial smooth-muscle cells (PASMCs) may play a role in HPV, and considerable evidence now supports that levels of reactive oxygen species (ROS) are paradoxically increased in PASMC under hypoxia, we investigated whether redox activation of RyRs by ROS may transduce HPV. By reverse transcriptase-polymerase chain reaction, we found that all three RyR isoforms are expressed in rat pulmonary arteries and in PASMCs. The sustained phase, but not the transient phase, of HPV can be prevented by pretreating pulmonary arteries with RyR inhibitors ryanodine (200 micromol/L) or dantrolene (50 micromol/L). The addition of dantrolene, ryanodine or the thiol-reducing agent dithiothreitol (1 mmol/L) during the sustained phase of HPV reversed the hypoxic vasoconstriction. In contrast, the superoxide scavenger nitroblue tetrazolium (500 nmol/L) prevented further hypoxic pulmonary vasoconstriction during the sustained phase of HPV but did not reverse it. Taken together, our data suggest that redox activation of RyRs by ROS has an important role in transducing the sustained contraction of pulmonary arteries under hypoxia.

Duke Scholars

Published In

Chest

DOI

ISSN

0012-3692

Publication Date

December 2005

Volume

128

Issue

6 Suppl

Start / End Page

556S / 558S

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Respiratory System
  • Rats, Wistar
  • Rats
  • Pulmonary Artery
  • Oxidation-Reduction
  • Nitroblue Tetrazolium
  • Male
 

Citation

APA
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ICMJE
MLA
NLM
Du, W., Frazier, M., McMahon, T. J., & Eu, J. P. (2005). Redox activation of intracellular calcium release channels (ryanodine receptors) in the sustained phase of hypoxia-induced pulmonary vasoconstriction. Chest, 128(6 Suppl), 556S-558S. https://doi.org/10.1378/chest.128.6_suppl.556S
Du, Wanglei, Melissa Frazier, Timothy J. McMahon, and Jerry P. Eu. “Redox activation of intracellular calcium release channels (ryanodine receptors) in the sustained phase of hypoxia-induced pulmonary vasoconstriction.Chest 128, no. 6 Suppl (December 2005): 556S-558S. https://doi.org/10.1378/chest.128.6_suppl.556S.
Du, Wanglei, et al. “Redox activation of intracellular calcium release channels (ryanodine receptors) in the sustained phase of hypoxia-induced pulmonary vasoconstriction.Chest, vol. 128, no. 6 Suppl, Dec. 2005, pp. 556S-558S. Pubmed, doi:10.1378/chest.128.6_suppl.556S.
Journal cover image

Published In

Chest

DOI

ISSN

0012-3692

Publication Date

December 2005

Volume

128

Issue

6 Suppl

Start / End Page

556S / 558S

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Respiratory System
  • Rats, Wistar
  • Rats
  • Pulmonary Artery
  • Oxidation-Reduction
  • Nitroblue Tetrazolium
  • Male