Role of cyclooxygenase-2 in the generation of vasoactive prostanoids in the rat pulmonary and systemic vascular beds

Syed R. Baber, Hunter C. Champion, Trinity J. Bivalacqua, Albert L. Hyman, Philip J. Kadowitz

Research output: Contribution to journalArticle

Abstract

Background - Prostanoid synthesis by the cyclooxygenase (COX)-2 pathway plays an important role in inflammation, and recent studies have shown the presence of COX-2 in the normal rat lung. However, the role of COX-2 in the generation of vasoactive prostanoids in the rat is uncertain. In the present study, the hypothesis that synthesis of vasoactive prostanoids via the COX-2 pathway can alter pulmonary and systemic vascular resistance was investigated, and the effects of selective COX-2 inhibitors on pulmonary and systemic responses to the prostanoid precursor arachidonic acid were examined in the anesthetized rat with a recently developed right-heart catheterization technique. Methods and Results - Injections of arachidonic acid caused dose-related increases in pulmonary vascular resistance and decreases in systemic vascular resistance. These responses were attenuated by selective COX-2 inhibitors and a selective COX-1 inhibitor, whereas responses to exogenous prostanoids were not altered. Nimesulide or NS-398 did not alter arachidonic acid-induced platelet aggregation in rat platelet-rich plasma. Western blot analysis and immunostaining showed the expression of both COX isoforms in the rat lung. Conclusions - The results of these experiments suggest that arachidonic acid is converted into vasoactive prostanoids by the COX-2 and COX-1 pathway in the pulmonary and peripheral vascular beds in the rat and that TXA2 is a major prostanoid formed in the normal rat lung.

Original languageEnglish (US)
Pages (from-to)896-901
Number of pages6
JournalCirculation
Volume108
Issue number7
DOIs
StatePublished - Aug 19 2003
Externally publishedYes

Keywords

  • Enzymes
  • Lung
  • Prostaglandins
  • Rat
  • Thromboxane

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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