Faculty Collaboration Database

Effects of chronic cytochrome P-450 inhibition on the course of hypertension and end-organ damage in Ren-2 transgenic rats. Vascul Pharmacol 2007;47(2-3):145-59

Date

07/03/2007

Pubmed ID

17604232

DOI

10.1016/j.vph.2007.05.005

Scopus ID

2-s2.0-34547100988 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

The aim of the present study was to evaluate the effects of inhibition of cytochrome P-450 (CYP) activity by 1-aminobenzotriazole (ABT) and by CoCl(2), first, on the development of hypertension when treatment was started in young male heterozygous Ren-2 transgenic rats (TGR) and, second, on blood pressure (BP) when treatment was started in adult TGR with established hypertension. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. In addition, the renal cortical activities of omega-hydroxylase, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of epoxygenase, the enzyme responsible for epoxyeicosatrienoic acids (EETs) production, and urinary excretion of 20-HETE and EETs in TGR and HanSD rats were assessed. TGR have higher renal tissue omega-hydroxylase activity and urinary excretion of 20-HETE but have significantly lower renal epoxygenase activity and urinary excretion of EETs than HanSD rats. Treatment of young TGR with ABT and CoCl(2) attenuated the development of hypertension and cardiac hypertrophy and prevented glomerulosclerosis. Administration of ABT and CoCl(2) in adult TGR decreased BP, cardiac hypertrophy, but did not reduce glomerulosclerosis. Our data suggest that altered production and/or action of CYP-derived metabolites play a permissive role in the development and maintenance of hypertension in TGR by enhancing ANG II-induced vasoconstriction.

Author List

Chábová VC, Kramer HJ, Vanecková I, Vernerová Z, Eis V, Tesar V, Skaroupková P, Thumová M, Schejbalová S, Husková Z, Vanourková Z, Kolský A, Imig JD, Cervenka L

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

Animals
Blood Pressure
Cardiomegaly
Cobalt
Cytochrome P-450 CYP4A
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Disease Models, Animal
Enzyme Inhibitors
Glomerulosclerosis, Focal Segmental
Heterozygote
Hydroxyeicosatetraenoic Acids
Hypertension
Kidney Cortex
Male
Oxygenases
Random Allocation
Rats
Rats, Sprague-Dawley
Renin
Renin-Angiotensin System
Triazoles
Vasoconstriction