Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs

Alan H. Stephenson, Randy S. Sprague, Neal Lee Weintraub, Lorraine McMurdo, Andrew J. Lonigro

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The intravenous administration of ethchlorvynol (ECV), in dogs, resulted in an acute lung injury (ALI) characterized by a 200 ± 80% increase in venous admixture and a 142 ± 30% increase in extravascular lung water (EVLW). Pretreatment with the cytochrome P-450 inhibitor 8-methoxypsoralen prevented the ECV-induced increase in venous admixture but not the increased EVLW. These findings parallel those reported for cyclooxygenase inhibition in ECV-induced ALI and suggest that an arachidonic acid (AA) metabolite of pulmonary cytochrome P-450 activity may mediate the increase in venous admixture of ALI. We demonstrate that canine pulmonary microsomes metabolize [1-14C]AA to a variety of products, including the cytochrome P-450 metabolites 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). In prostaglandin F(2α)-contracted, isolated pulmonary venous rings, 5,6-EET induced relaxation in a concentration-dependent manner. This action of 5,6- EET was prevented by indomethacin (10-5 M). These results suggest that 5,6- EET may serve as the cyclooxygenase-dependent endogenous pulmonary vasodilator responsible for the increase in venous admixture of ECV-induced ALI.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number4 39-4
StatePublished - May 13 1996
Externally publishedYes

Fingerprint

Ethchlorvynol
Acute Lung Injury
Cytochrome P-450 Enzyme System
Extravascular Lung Water
Dogs
Lung
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Methoxsalen
Prostaglandins F
Microsomes
Vasodilator Agents
Indomethacin
Intravenous Administration
Canidae
Hypoxia
5,6-epoxy-8,11,14-eicosatrienoic acid

Keywords

  • 8- methoxypsoralen
  • arachidonic acid
  • cyclooxygenase
  • epoxyeicosatrienoic acid
  • extravascular lung water
  • microsomes
  • pulmonary vein
  • venous admixture

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs. / Stephenson, Alan H.; Sprague, Randy S.; Weintraub, Neal Lee; McMurdo, Lorraine; Lonigro, Andrew J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 270, No. 4 39-4, 13.05.1996.

Research output: Contribution to journalArticle

Stephenson, Alan H. ; Sprague, Randy S. ; Weintraub, Neal Lee ; McMurdo, Lorraine ; Lonigro, Andrew J. / Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs. In: American Journal of Physiology - Heart and Circulatory Physiology. 1996 ; Vol. 270, No. 4 39-4.
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