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[PMID]: | 8967376 |
[Au] Autor: | Stephenson AH; Sprague RS; Weintraub NL; McMurdo L; Lonigro AJ |
[Ad] Endereço: | Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, Missouri 63104, USA. |
[Ti] Título: | Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs. |
[So] Source: | Am J Physiol;270(4 Pt 2):H1355-62, 1996 Apr. | [Is] ISSN: | 0002-9513 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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-(14)C]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 F2 alpha-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 may serve as the cyclooxygenase-dependent endogenous pulmonary vasodilator responsible for the increase in venous admixture of ECV-induced ALI. |
[Mh] Termos MeSH primário: |
Inibidores das Enzimas do Citocromo P-450 Hipóxia/etiologia Hipóxia/fisiopatologia Lesão Pulmonar
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[Mh] Termos MeSH secundário: |
Ácido 8,11,14-Eicosatrienoico/análogos & derivados Ácido 8,11,14-Eicosatrienoico/metabolismo Ácido 8,11,14-Eicosatrienoico/farmacologia Animais Dinoprosta/farmacologia Cães Etclorvinol/farmacologia Pulmão/efeitos dos fármacos Pulmão/metabolismo Masculino Metoxaleno/farmacologia Microssomos/metabolismo Veículos Farmacêuticos/farmacologia Vasoconstrição/efeitos dos fármacos
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S. |
[Nm] Nome de substância:
| 0 (Cytochrome P-450 Enzyme Inhibitors); 0 (Pharmaceutical Vehicles); 6EIM3851UZ (Ethchlorvynol); 7324-41-6 (8,11,14-Eicosatrienoic Acid); 81246-84-6 (5,6-epoxy-8,11,14-eicosatrienoic acid); B7IN85G1HY (Dinoprost); U4VJ29L7BQ (Methoxsalen) |
[Em] Mês de entrada: | 9612 |
[Cu] Atualização por classe: | 161123 |
[Lr] Data última revisão:
| 161123 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 960401 |
[St] Status: | MEDLINE |
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