Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C

Ben M. Tsai, Meijing Wang, Jeffrey M. Pitcher, Kirstan K. Meldrum, Daniel R. Meldrum

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Pulmonary arteries exhibit a marked vasoconstriction when exposed to hypoxic conditions. Although this may be an adaptive response to match lung ventilation with perfusion, the potential consequences of sustained pulmonary vasoconstriction include pulmonary hypertension and right heart failure. Concomitant production of proinflammatory mediators during hypoxia may exacerbate acute increases in pulmonary vascular resistance. We hypothesized that acute hypoxia causes pulmonary arterial contraction and increases the pulmonary artery tissue expression of proinflammatory cytokines via a protein kinase C (PKC)-mediated mechanism. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings during hypoxia in the presence and absence of the PKC inhibitors calphostin C or chelerythrine. In separate experiments, pulmonary artery rings were treated with the PKC activator thymeleatoxin for 60 min. After hypoxia, with or without PKC inhibition, or PKC activation alone, pulmonary artery rings were subjected to mRNA analysis for TNF-α and IL-1β via RT-PCR. Our results showed that, in isolated pulmonary arteries, hypoxia caused a biphasic contraction and increased expression of TNF-α and IL-1β mRNA. Both effects were inhibited by PKC inhibition. PKC activation resulted in pulmonary artery contraction and increased the pulmonary artery expression of TNF-α and IL-1β mRNA. These findings suggest that hypoxia induces the expression of inflammatory cytokines and causes vasoconstriction via a PKC-dependent mechanism. We conclude that PKC may have a central role in modulating hypoxic pulmonary vasoconstriction, and further elucidation of its involvement may lead to therapeutic application.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number6 31-6
DOIs
StatePublished - Dec 2004

Fingerprint

Vasoconstriction
Protein Kinase C
Pulmonary Artery
Cytokines
Lung
Interleukin-1
Messenger RNA
Protein C Inhibitor
Protein Kinase Inhibitors
Pulmonary Hypertension
Vascular Resistance
Ventilation
Hypoxia
Heart Failure
Perfusion
Polymerase Chain Reaction

Keywords

  • Hypoxia
  • Inflammation
  • Pulmonary hypertension
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C. / Tsai, Ben M.; Wang, Meijing; Pitcher, Jeffrey M.; Meldrum, Kirstan K.; Meldrum, Daniel R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 287, No. 6 31-6, 12.2004.

Research output: Contribution to journalArticle

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