15(S)-15-Methyl prostaglandin F(2α) elicits marked peripheral airway constriction in the intact dog

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

Research output: Contribution to journalArticle

Abstract

The 15-methyl analog of the prostaglandin (PG) F(2α) has been used clinically as an abortifacient agent. In the present study, the bronchopulmonary and cardiopulmonary effects of intravenously administered analog were investigated in 26 anesthetized, paralyzed dogs and compared to those of the naturally occurring parent compound, PFG(2α). The analog produced a dose-related increase in lung resistance and decrease in dynamic compliance. Functional residual capacity and specific conductance were significantly decreased at the peak of the airway response; arterial oxygen tension appeared unchanged. The effects of the analog on pulmonary mechanics were accompanied by a marked, dose-related increase in pulmonary arterial pressure. Aortic pressure and cardiac output were unchanged. The activity of PGF(2α) in the airways and vascular system was quantitatively similar, but smaller in magnitude and duration, than that of the analog. The airway responses to PGF(2α) and the analog were significantly reduced, but not abolished, by atropine. Left ventricular administration of the analog diminished its airway effects. In six dogs breathing spontaneously, the analog increased respiratory rate and decreased tidal volume. These results suggest that 15-methyl PGF(2α) has marked effects on both the airways and pulmonary vascular bed, with peripheral airways being especially responsive. A cholinergic reflex may contribute to the airway effects. These findings demonstrate that this agent has pronounced bronchopulmonary actions and suggest caution in its use in induction of mid-trimester abortion.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume207
Issue number1
StatePublished - Dec 1 1978

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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