|2,3',4,5'-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P-450 1B1.|
|PMID: 20852048 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-17|
|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|
|Created Date: 2010-12-03 Completed Date: 2011-01-13 Revised Date: 2012-01-24|
Medline Journal Info:
|Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States|
|Languages: eng Pagination: H1891-901 Citation Subset: IM|
|Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Antihypertensive Agents / pharmacology*
Aorta / drug effects, enzymology
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*, metabolism
Blood Pressure / drug effects*
Cardiomegaly / enzymology, physiopathology, prevention & control
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
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
Sodium Chloride, Dietary*
Stilbenes / pharmacology*
Superoxides / metabolism
Vasoconstriction / drug effects
Vasodilation / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism
|R01-HL19134-35/HL/NHLBI NIH HHS|
|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 220.127.116.11/Aryl Hydrocarbon Hydroxylases; EC 18.104.22.168/cytochrome P450, family 1, subfamily B, polypeptide 1; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.99.-/NADPH oxidase 1; EC 22.214.171.124/Mitogen-Activated Protein Kinase 1; EC 126.96.36.199/Mitogen-Activated Protein Kinase 3; EC 188.8.131.52/p38 Mitogen-Activated Protein Kinases|
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