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 language | English (US) |
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Pages (from-to) | H1355-H1362 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 270 |
Issue number | 4 39-4 |
DOIs | |
State | Published - 1996 |
Externally published | Yes |
Keywords
- 8- methoxypsoralen
- arachidonic acid
- cyclooxygenase
- epoxyeicosatrienoic acid
- extravascular lung water
- microsomes
- pulmonary vein
- venous admixture
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)