Document Detail


Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.
MedLine Citation:
PMID:  21300669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.
Authors:
Sandra L Pfister
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-07
Journal Detail:
Title:  Hypertension     Volume:  57     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-17     Completed Date:  2011-07-04     Revised Date:  2013-05-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  825-32     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. spfister@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Arachidonate Lipoxygenases / metabolism*
Arachidonic Acid / metabolism*,  pharmacology
Blotting, Western
Endothelium, Vascular / drug effects,  metabolism*
Female
Hydroxyeicosatetraenoic Acids / metabolism*,  pharmacology
Male
Mass Spectrometry
Pulmonary Artery / drug effects,  physiology*
Rabbits
Sex Factors
Vasoconstriction / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
HL093181/HL/NHLBI NIH HHS; R21 HL093181/HL/NHLBI NIH HHS; R21 HL093181-01A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 506-32-1/Arachidonic Acid; EC 1.13.11.-/Arachidonate Lipoxygenases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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