Document Detail


Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue.
MedLine Citation:
PMID:  9176244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on human pulmonary arterial tone. 20-HETE elicited a dose-dependent and indomethacin-inhibitable vasodilation of isolated small pulmonary arteries. Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids. Indomethacin blocked formation of prostanoids without effects on the conversion of arachidonate into 20-HETE, 20-HETE was converted by lung microsomes into prostanoids, raising the possibility that 20-HETE may be metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory compound. Western blots probed with a polyclonal antibody to cP450 4A identified a protein of approximately 50 kDa immunologically similar to the cP450 4A in rat liver. We conclude that small arteries from human lungs dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and that the proteins and enzymatic activity required to synthesize this product are present in lungs. Our observations suggest that cP450 enzyme products could be endogenous modulators of pulmonary vascular tone.
Authors:
E K Birks; M Bousamra; K Presberg; J A Marsh; R M Effros; E R Jacobs
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  272     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-08     Completed Date:  1997-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L823-9     Citation Subset:  IM    
Affiliation:
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / metabolism
Cats
Cattle
Dose-Response Relationship, Drug
Eicosanoids / metabolism
Female
Ferrets
Humans
Hydroxyeicosatetraenoic Acids / pharmacology*
Lung / metabolism
Male
Middle Aged
Pulmonary Artery / drug effects*
Rabbits
Rats
Vasodilation*
Grant Support
ID/Acronym/Agency:
5M0 1RR-00058/RR/NCRR NIH HHS; HL-49294/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Eicosanoids; 0/Hydroxyeicosatetraenoic Acids; 506-32-1/Arachidonic Acid; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid

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