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rdf:type |
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lifeskim:mentions |
umls-concept:C0010762,
umls-concept:C0014257,
umls-concept:C0017262,
umls-concept:C0020538,
umls-concept:C0046616,
umls-concept:C0185117,
umls-concept:C0220781,
umls-concept:C0277785,
umls-concept:C1801960,
umls-concept:C1880177,
umls-concept:C1883254,
umls-concept:C2911684
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pubmed:issue |
1
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pubmed:dateCreated |
2007-6-21
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pubmed:abstractText |
Epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. It has been shown that 5alpha-dihydrotestosterone (DHT) administration (56 mg/kg of body weight per day IP for 14 days) increases blood pressure, cytochrome P450 4A expression, and 20-hydroxyeicosatetraenoic acid synthesis in rats. We examined whether increased vascular 20-hydroxyeicosatetraenoic acid synthesis underlies endothelial dysfunction and hypertension in DHT-treated male Sprague-Dawley rats by using HET0016, a selective cytochrome P450 4A inhibitor. Coadministration of HET0016 (10 mg/kg per day IP for 14 days) to DHT-treated rats markedly reduced DHT-induced interlobar arterial production of 20-hydroxyeicosatetraenoic acid (14.3+/-1.5 versus 1.5+/-0.5 ng/mg of protein per hour; P<0.05), superoxide anion (246+/-47 versus 31+/-8 cpm/microg of protein), and the levels of gp91-phox, p47-phox, and 3-nitrosylated proteins. Moreover, the maximal relaxing response to acetylcholine in phenylephrine-preconstricted renal interlobar arteries from DHT-treated rats (42.8+/-4.8%) significantly (P<0.05) increased in the presence of HET0016 (81.5+/-10.8%). Importantly, the administration of HET0016 negated DHT-induced hypertension; systolic blood pressure was reduced from 146+/-2 mm Hg in DHT-treated rats to 130+/-1 mm Hg (P<0.05). The results strongly implicate vascular cytochrome P450 4A-derived 20-hydroxyeicosatetraenoic acid in the development of androgen-induced endothelial dysfunction and hypertension.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/20-hydroxy-5,8,11,14-eicosatetraenoi...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Alkane 1-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Amidines,
http://linkedlifedata.com/resource/pubmed/chemical/Cybb protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydrotestosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-hydroxy-N'-(4-butyl-2-methylphenyl...,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/neutrophil cytosolic factor 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1524-4563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
123-9
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17548721-Acetylcholine,
pubmed-meshheading:17548721-Alkane 1-Monooxygenase,
pubmed-meshheading:17548721-Amidines,
pubmed-meshheading:17548721-Animals,
pubmed-meshheading:17548721-Blood Pressure,
pubmed-meshheading:17548721-Dihydrotestosterone,
pubmed-meshheading:17548721-Drug Synergism,
pubmed-meshheading:17548721-Endothelium, Vascular,
pubmed-meshheading:17548721-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:17548721-Hypertension,
pubmed-meshheading:17548721-Male,
pubmed-meshheading:17548721-Membrane Glycoproteins,
pubmed-meshheading:17548721-NADPH Oxidase,
pubmed-meshheading:17548721-Oxidative Stress,
pubmed-meshheading:17548721-Rats,
pubmed-meshheading:17548721-Rats, Sprague-Dawley,
pubmed-meshheading:17548721-Renal Artery,
pubmed-meshheading:17548721-Superoxides,
pubmed-meshheading:17548721-Vasodilation,
pubmed-meshheading:17548721-Vasodilator Agents
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pubmed:year |
2007
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pubmed:articleTitle |
Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension.
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pubmed:affiliation |
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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