Faculty Collaboration Database

Involvement of cytochrome P-450 1B1 in renal dysfunction, injury, and inflammation associated with angiotensin II-induced hypertension in rats. Am J Physiol Renal Physiol 2012 Feb 15;302(4):F408-20

Date

11/18/2011

Pubmed ID

22088434

Pubmed Central ID

PMC3289420

DOI

10.1152/ajprenal.00542.2011

Scopus ID

2-s2.0-84856690531 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

We investigated the contribution of cytochrome P-450 1B1 (CYP1B1) to renal dysfunction and organ damage associated with ANG II-induced hypertension in rats. ANG II (300 ng·kg(-1)·min(-1)) or vehicle were infused for 2 wk, with daily injections of a selective CYP1B1 inhibitor, 2,4,3',5'-tetramethoxystilbene (TMS; 300 μg/kg ip), or its vehicle. ANG II increased blood pressure and renal CYP1B1 activity that were prevented by TMS. ANG II also increased water intake and urine output, decreased glomerular filtration rate, increased urinary Na(+) and K(+) excretion, and caused proteinuria, all of which were prevented by TMS. ANG II infusion caused hypertrophy, endothelial dysfunction, and increased reactivity of renal and interlobar arteries to vasoconstrictor agents and renal vascular resistance and interstitial fibrosis as indicated by accumulation of α-smooth muscle actin, fibronectin, and collagen, and inflammation as indicated by increased infiltration of CD-3(+) cells; these effects were inhibited by TMS. ANG II infusion also increased production of reactive oxygen species (ROS) and activities of NADPH oxidase, ERK1/2, p38 MAPK, and c-Src that were prevented by TMS. TMS alone had no effect on any of the above parameters. These data suggest that CYP1B1 contributes to the renal pathophysiological changes associated with ANG II-induced hypertension, most likely via increased ROS production and activation of ERK1/2, p38 MAPK, and c-Src and that CYP1B1 could serve as a novel target for treating renal disease associated with hypertension.

Author List

Jennings BL, Anderson LJ, Estes AM, Fang XR, Song CY, Campbell WB, Malik KU

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Aryl Hydrocarbon Hydroxylases
Blood Pressure
Cytochrome P-450 CYP1B1
Endothelium, Vascular
Hemodynamics
Hypertension, Renal
Inflammation
Kidney
Male
NADPH Oxidases
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Signal Transduction
Stilbenes