TNF-α induced bronchial vasoconstriction

Elizabeth M. Wagner

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


The pro-inflammatory characteristics of tumor necrosis factor-α (TNF-α) have been extensively characterized in in vitro systems. Furthermore, this cytokine has been shown to play a pivotal role in airways inflammation in asthma. Since the airway vasculature also performs an essential function in inflammatory cell transit to the airways, experiments were performed to determine the effects of TNF-α on bronchial vascular resistance (BVR). In anesthetized, ventilated sheep, the bronchial artery (BA) was cannulated and perfused with autologous blood. BVR was defined as inflow pressure/flow and averaged 6.3 ± 0.2 mmHg·ml-1. min-1 (±SE) for the 25 sheep studied. Recombinant human TNF-α (10 μg for 20 or 40 min) infused directly into the BA resulted in a significant decrease in BVR to 87% of baseline (P < 0.05). This vasodilation was followed by a reversal of tone by 120 min and a sustained increase in BVR to 126% of baseline (P < 0.05). Since others have shown TNF-α caused coronary vasoconstriction through endothelial release of endothelin-1 (ET-1), an ET-1 antagonist was used to block bronchial vasoconstriction. BQ-123, a selective ET(A) receptor antagonist, was delivered to the bronchial vasculature prior to TNF-α challenge. Attenuation of bronchial vasoconstriction was observed at 120 min (P < 0.03). Thus TNF-α causes bronchial vasoconstriction by the secondary release of ET-1. Although TNF-α exerts pro-inflammatory actions on most cells of the airways, vasoactive properties of this cytokine likely further contribute to the inflammatory status of the airways.

Original languageEnglish (US)
Pages (from-to)H946-H951
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 48-3
StatePublished - 2000


  • Airways resistance
  • Bronchial artery
  • Endothelin-1
  • Inflammation
  • Sheep
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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