Mepacrine attenuates pulmonary vasoreactivity in rabbits

Jay R. Shayevitz, A. J. McShane, R. J. Traystman, G. H. Gurtner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The organic peroxide tert-butyl hydroperoxide (t-bu-OOH) induces pulmonary vasoconstriction by stimulating production of thromboxane in the rabbit lung, possibly by activating phospholipase A2. t-bu-OOH-induced vasoconstriction and thromboxane production is augmented by inhalational anesthetic agents, perhaps due to an effect of anesthetic agents on membrane lipids. To further investigate the mechanism of thromboxane generation, we studied the influence of the phospholipase A2 inhibitor, mepacrine, in a dose known to inhibit the enzyme in other systems, on t-bu-OOH-induced pulmonary arterial vasoconstriction. We found that 10-4 M mepacrine completely inhibited t-bu-OOH induced vasoconstriction. We also found that mepacrine inhibited arachidonic acid-induced pulmonary vasoconstriction but did not inhibit thromboxane productions. We also investigated the effect of mepacrine on two other pulmonary vasoconstrictors, angiotensin II (ANG II) and KCl, which do not act through arachidonic acid metabolites in the rabbit lung. Mepacrine inhibited both ANG-II and KCl-induced vasoconstriction. The inhibition by mepacrine of pulmonary vasoconstriction is reversible if the drug is washed out of the lung. This effect of mepacrine cannot be explained by phospholipase inhibition alone and is consistent with prevention of smooth muscle contraction.

Original languageEnglish (US)
Pages (from-to)1921-1926
Number of pages6
JournalJournal of Applied Physiology
Volume66
Issue number4
StatePublished - 1989
Externally publishedYes

Fingerprint

Quinacrine
Vasoconstriction
Rabbits
Lung
Thromboxanes
Arachidonic Acid
Anesthetics
tert-Butylhydroperoxide
Phospholipases
Phospholipases A2
Peroxides
Vasoconstrictor Agents
Membrane Lipids
Muscle Contraction
Angiotensin II
Smooth Muscle
Enzymes

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Shayevitz, J. R., McShane, A. J., Traystman, R. J., & Gurtner, G. H. (1989). Mepacrine attenuates pulmonary vasoreactivity in rabbits. Journal of Applied Physiology, 66(4), 1921-1926.

Mepacrine attenuates pulmonary vasoreactivity in rabbits. / Shayevitz, Jay R.; McShane, A. J.; Traystman, R. J.; Gurtner, G. H.

In: Journal of Applied Physiology, Vol. 66, No. 4, 1989, p. 1921-1926.

Research output: Contribution to journalArticle

Shayevitz, JR, McShane, AJ, Traystman, RJ & Gurtner, GH 1989, 'Mepacrine attenuates pulmonary vasoreactivity in rabbits', Journal of Applied Physiology, vol. 66, no. 4, pp. 1921-1926.
Shayevitz JR, McShane AJ, Traystman RJ, Gurtner GH. Mepacrine attenuates pulmonary vasoreactivity in rabbits. Journal of Applied Physiology. 1989;66(4):1921-1926.
Shayevitz, Jay R. ; McShane, A. J. ; Traystman, R. J. ; Gurtner, G. H. / Mepacrine attenuates pulmonary vasoreactivity in rabbits. In: Journal of Applied Physiology. 1989 ; Vol. 66, No. 4. pp. 1921-1926.
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