| Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits. | |
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MedLine Citation:
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PMID: 21300669 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sandra L Pfister |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-07 |
Journal Detail:
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Title: Hypertension Volume: 57 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-07-04 Revised Date: 2013-05-26 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 825-32 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. spfister@mcw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL093181/HL/NHLBI NIH HHS; R21 HL093181/HL/NHLBI NIH HHS; R21 HL093181-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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