Contribution of cytochrome P450 1B1 to hypertension and associated pathophysiology: a novel target for antihypertensive agents.
The aim of this review is to discuss the contribution of cytochrome P450 (CYP) 1B1 in vascular smooth muscle cell growth, hypertension, and associated pathophysiology. CYP1B1 is expressed in cardiovascular and renal tissues, and mediates angiotensin II (Ang II)-induced activation of NADPH oxidase and generation of reactive oxygen species (ROS), and vascular smooth muscle cell migration, proliferation, and hypertrophy. Moreover, CYP1B1 contributes to the development and/or maintenance of hypertension produced by Ang II-, deoxycorticosterone (DOCA)-salt-, and N(ω)-nitro-L-arginine methyl ester-induced hypertension and in spontaneously hypertensive rats. The pathophysiological changes, including cardiovascular hypertrophy, increased vascular reactivity, endothelial and renal dysfunction, injury and inflammation associated with Ang II- and/or DOCA-salt induced hypertension in rats, and Ang II-induced hypertension in mice are minimized by inhibition of CYP1B1 activity with 2,4,3',5'-tetramethoxystilbene or by Cyp1b1 gene disruption in mice. These pathophysiological changes appear to be mediated by increased production of ROS via CYP1B1-dependent NADPH oxidase activity and extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Src.
Department of Pharmacology, College of Medicine, 874 Union Avenue, University of Tennessee Health Science Center, Memphis, TN 38163, USA. kmalik@uthsc.edu
Kafait U
KU
Malik
Brett L
BL
Jennings
Fariborz A
FA
Yaghini
Seyhan
S
Sahan-Firat
Chi Young
CY
Song
Anne M
AM
Estes
Xiao R
XR
Fang
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology
D000959:Antihypertensive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System