Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology

Brett L. Jennings, Seyhan Sahan-Firat, Anne M. Estes, Kanak Das, Nasreen Farjana, Xiao R. Fang, Frank J. Gonzalez, Kafait Malik

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)667-674
Number of pages8
JournalHypertension
Volume56
Issue number4
DOIs
StatePublished - Oct 1 2010

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Angiotensin II
Cytochrome P-450 Enzyme System
Hypertension
Blood Vessels
Cardiovascular Diseases
Blood Pressure
Cardiomegaly
Vasoconstrictor Agents
Vascular Smooth Muscle
Smooth Muscle Myocytes
Reactive Oxygen Species
Peptides
Growth

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology. / Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Gonzalez, Frank J.; Malik, Kafait.

In: Hypertension, Vol. 56, No. 4, 01.10.2010, p. 667-674.

Research output: Contribution to journalArticle

Jennings, Brett L. ; Sahan-Firat, Seyhan ; Estes, Anne M. ; Das, Kanak ; Farjana, Nasreen ; Fang, Xiao R. ; Gonzalez, Frank J. ; Malik, Kafait. / Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology. In: Hypertension. 2010 ; Vol. 56, No. 4. pp. 667-674.
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