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.