Dependence of the airway and pulmonary vascular effects of arachidonic acid upon route and rate of administration

E. W. Spannhake, A. L. Hyman, P. J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

The opposing pulmonary constrictor and dilator effects of the prostaglandin precursor, arachidonic acid (AA), were investigated in anesthetized dogs. Administration of AA aerosol to vagotomized animals produced bronchoconstriction associated with an increase in airway resistance and a decrease in dynamic compliance. These airway effects were seen in the absence of pulmonary vasoconstriction and were abolished by the cyclooxygenase inhibitor, indomethacin. In contrast to the bronchoconstriction and pulmonary vasoconstriction produced by i.v. administration of AA by rapid bolus injection, slow i.v. infusion produced dose-related decreases in pulmonary arterial pressure. In the presence of enhanced airway and vascular tone, AA also decreased pulmonary vascular resistance, but had no effect on airway resistance or dynamic compliance. Under conditions of constant flow in the isolated lobe of the intact chest dog, AA infusion produced a dose-related vasodilation in all animals when vascular tone was pharmacologically enhanced. In two of five animals, vasodilation changed to vasoconstriction at the higher infusion rates. These data suggest that the airways can respond to locally synthesized prostanoids independently from the pulmonary vessels. They also suggest that the pulmonary vascular effect of i.v. AA can be either constrictor or dilator, depending upon the concentration of precursor made available. Synthesis from AA of the pulmonary vasodilator prostanoid, most likely PGI2, appears to have minimal pulmonary vascular effect unless pulmonary vascular tone is enhanced.

Original languageEnglish (US)
Pages (from-to)584-590
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume212
Issue number3
StatePublished - Jan 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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