Evidence for modification of pulmonary cyclooxygenase activity by endotoxin in the dog

E. W. Spannhake, J. L. Colombo, P. A. Craigo, D. B. McNamara, A. L. Hyman, P. J. Kadowitz

Research output: Contribution to journalArticle

Abstract

Pulmonary responses to endotoxin administration have been associated with increased synthesis of products derived from arachidonic acid (AA). Little is currently known about the effects of endotoxin on the activities of the various enzymes of the AA metabolic pathways. To investigate these activities, we increased the availability of AA in vivo by iv administration to anesthetized vagotomized dogs before and 2 h after endotoxin. In addition, enzyme activities were assayed directly in microsomal and high-speed supernatant preparations of lung parenchyma from normal and endotoxin-treated dogs. Rapid iv injection of AA (1-6 mg) produced a characteristic dose-related increase in lung resistance and pulmonary arterial pressure and decrease in dynamic lung compliance. After endotoxin, responses were significantly enhanced at all doses of the precursor. The bronchopulmonary effects of exogenously administered prostanoids were not altered following endotoxin. Enhanced responses to AA were not attributable to synthesis of bronchoconstrictive leukotrienes, since cyclooxygenase blockade abolished all responses to AA in the lung. The contribution of thromboxane A2 to the effects of AA appeared to be proportionately similar in normal and endotoxin-treated animals, based on blockade of thromboxane synthesis. The action of endotoxin on AA metabolism was independent of the presence of leukocytes. Neither synthesis of prostanoids from prostaglandin H2 (PGH2) by terminal enzymes in lung preparations nor the activity of 15-hydroxyprostaglandin dehydrogenase was altered in endotoxin-treated dogs. The current data are most consistent with the hypothesis that endotoxemia facilitates synthesis of prostaglandins by increasing the availability of PGH2 to the terminal enzymes by enhancing cyclooxygenase activity.

Original languageEnglish (US)
Pages (from-to)191-198
Number of pages8
JournalJournal of Applied Physiology Respiratory Environmental and Exercise Physiology
Volume54
Issue number1
StatePublished - May 26 1983

    Fingerprint

ASJC Scopus subject areas

  • Physiology
  • Endocrinology

Cite this