Modification of pulmonary vascular responses to arachidonic acid by alterations in physiologic state

A. L. Hyman, A. A. Mathe, C. A. Leslie, C. C. Matthews, J. T. Bennett, E. W. Spannhake, P. J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of bolus injections of arachidonic acid and prostaglandins (PG) E 2 and F 2α on the pulmonary vascular bed were compared under resting conditions and after alteration in the physiologic state of the lung. Studies were carried out in the vascularly isolated lung lobe of the intact, anesthetized dog under conditions of controlled blood flow. Arachidonic acid, PGE 2 and PGF 2α increased pulmonary vascular resistance by constricting intrapulmonary veins and arteries in a dose-related manner, as did an analog of the endoperoxide, PGH 2, whereas PGI 2 dilated the pulmonary bed. The response to arachidonate was associated with a 2- to 3-fold increase in levels of PGE- and PGF-like substances in pulmonary venous blood and was blocked by indomethacin. The effects of arachidonic acid, but not the PGs, were greatly enhanced during perfusion with either dextran or saline and the enhanced response in saline was associated with a 15- to 20-fold increase in levels of PG-like substances in the pulmonary effluent. Responses to arachidonate were not dependent upon the presence of formed elements in blood but were related to perfusate protein concentration. Alveolar hypoxia decreased responses to the precursor while those to PGE 2 and PGF 2α were enhanced. Responses to the PGs, but not those to arachidonate, were affected by changes in blood pH. Sublethal doses of Escherichia coli endotoxin increased the response to arachidonic acid, but not those to PGE 2 and PGF 2α. Results of the present study indicate that the effects of bolus injection of arachidonic acid on the pulmonary vascular bed are due mainly to formation of constrictor metabolites which may overshadow the actions of any dilator (PGI 2) formed and suggest that metabolism of the precursor is altered by changes in physiologic state.

Original languageEnglish (US)
Pages (from-to)388-401
Number of pages14
JournalJournal of Pharmacology and Experimental Therapeutics
Volume207
Issue number2
StatePublished - Dec 1 1978
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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