| 2,3',4,5'-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P-450 1B1. | |
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MedLine Citation:
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PMID: 20852048 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reactive oxygen species (ROS) contribute to various models of hypertension, including deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Recently, we have shown that ROS, generated by cytochrome P-450 1B1 (CYP1B1) from arachidonic acid, mediate vascular smooth muscle cell growth caused by angiotensin II. This study was conducted to determine the contribution of CYP1B1 to hypertension and associated pathophysiological changes produced by DOCA (30 mg/kg) given subcutaneously per week with 1% NaCl + 0.1% KCl in drinking water to uninephrectomized rats for 6 wk. DOCA-salt treatment increased systolic blood pressure (SBP). Injections of the selective inhibitor of CYP1B1, 2,3',4,5'-tetramethoxystilbene (TMS; 300 μg/kg ip every 3rd day) initiated at the 4th week of DOCA-salt treatment normalized SBP and decreased CYP1B1 activity but not its expression in the aorta, heart, and kidney. TMS also inhibited cardiovascular and kidney hypertrophy, prevented the increase in vascular reactivity and endothelial dysfunction, and minimized the increase in urinary protein and K(+) output and the decrease in urine osmolality, Na(+) output, and creatinine clearance associated with DOCA-salt treatment. These pathophysiological changes caused by DOCA-salt treatment and associated increase in vascular superoxide production, NADPH oxidase activity, and expression of NOX-1, and ERK1/2 and p38 MAPK activities in the aorta, heart, and kidney were inhibited by TMS. These data suggest that CYP1B1 contributes to DOCA-salt-induced hypertension and associated pathophysiological changes, most likely as a result of increased ROS production and ERK1/2 and p38 MAPK activity, and could serve as a novel target for the development of agents like TMS to treat hypertension. |
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Authors:
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Seyhan Sahan-Firat; Brett L Jennings; Fariborz A Yaghini; Chi Young Song; Anne M Estes; Xiao R Fang; Nasreen Farjana; Amir I Khan; Kafait U Malik |
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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: 2010-09-17 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-03 Completed Date: 2011-01-13 Revised Date: 2012-01-24 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1891-901 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
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blood Animals Antihypertensive Agents / pharmacology* Aorta / drug effects, enzymology Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*, metabolism Blood Pressure / drug effects* Cardiomegaly / enzymology, physiopathology, prevention & control Desoxycorticosterone* Disease Models, Animal Diuresis / drug effects Endothelium, Vascular / drug effects, enzymology Enzyme Inhibitors / pharmacology* Hydroxyeicosatetraenoic Acids / blood Hypertension / enzymology, etiology, pathology, physiopathology, prevention & control* Kidney / drug effects, enzymology, pathology, physiopathology Male Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Muscle, Smooth, Vascular / drug effects, enzymology, physiopathology Myocardium / enzymology, pathology NADH, NADPH Oxidoreductases / metabolism Proteinuria / enzymology, physiopathology, prevention & control Rats Rats, Sprague-Dawley Sodium Chloride, Dietary* Stilbenes / pharmacology* Superoxides / metabolism Time Factors Vasoconstriction / drug effects Vasodilation / drug effects p38 Mitogen-Activated Protein Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL19134-35/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2,4,3',5'-tetramethoxystilbene; 0/Antihypertensive Agents; 0/Enzyme Inhibitors; 0/Hydroxyeicosatetraenoic Acids; 0/Sodium Chloride, Dietary; 0/Stilbenes; 11062-77-4/Superoxides; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 64-85-7/Desoxycorticosterone; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/cytochrome P450, family 1, subfamily B, polypeptide 1; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.99.-/NADPH oxidase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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