Cytochrome P450 1B1 Contributes To Angiotensin Ii-Induced Hypertension And Associated Pathophysiology
| Autor: | Kafait U. Malik, Xiao R. Fang, Anne M. Estes, Brett L. Jennings, Seyhan Sahan-Firat, Frank J. Gonzalez, Kanak Das, Nasreen Farjana |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Angiotensin receptor medicine.medical_specialty Vascular smooth muscle Blotting Western Blood Pressure Cardiomegaly Biology Article Rats Sprague-Dawley Mice Internal medicine Stilbenes Renin–angiotensin system Internal Medicine medicine Animals Vasoconstrictor Agents Endothelial dysfunction Infusions Intravenous Aorta Mice Knockout Angiotensin II receptor type 1 Angiotensin II Myocardium NADPH Oxidases Organ Size medicine.disease Rats Mice Inbred C57BL Blood pressure Endocrinology Pathophysiology of hypertension Cytochrome P-450 CYP1B1 Hypertension Aryl Hydrocarbon Hydroxylases Endothelium Vascular Mitogen-Activated Protein Kinases Reactive Oxygen Species |
| Popis: | Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study showing that angiotensin II–induced vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice (1000 μg/kg per day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased vascular reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor 2,3′,4,5′-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1 −/− mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II–induced hypertension and associated pathophysiological changes. Moreover, 2,3′,4,5′-tetramethoxystilbene, which prevents both cytochrome P450 1B1–dependent and –independent components of angiotensin II–induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases. |
| Databáze: | OpenAIRE |
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