Effects of chronic cytochrome P-450 inhibition on the course of hypertension and end-organ damage in Ren-2 transgenic rats
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
HL5699
NHLBI NIH HHS - United States
PubMed
17604232
DOI
10.1016/j.vph.2007.05.005
PII: S1537-1891(07)00094-8
Knihovny.cz E-resources
- MeSH
- Cytochrome P-450 CYP2J2 MeSH
- Cytochrome P-450 CYP4A metabolism MeSH
- Glomerulosclerosis, Focal Segmental physiopathology MeSH
- Heterozygote MeSH
- Hypertension physiopathology MeSH
- Cytochrome P-450 Enzyme Inhibitors * MeSH
- Enzyme Inhibitors pharmacology MeSH
- Cardiomegaly physiopathology MeSH
- Cobalt MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney Cortex MeSH
- Hydroxyeicosatetraenoic Acids biosynthesis MeSH
- Disease Models, Animal MeSH
- Random Allocation MeSH
- Oxygenases metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Renin-Angiotensin System physiology MeSH
- Renin genetics metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Triazoles pharmacology MeSH
- Vasoconstriction MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- 1-aminobenzotriazole MeSH Browser
- 20-hydroxy-5,8,11,14-eicosatetraenoic acid MeSH Browser
- cobaltous chloride MeSH Browser
- Cytochrome P-450 CYP2J2 MeSH
- Cytochrome P-450 CYP4A MeSH
- Cytochrome P-450 Enzyme Inhibitors * MeSH
- Enzyme Inhibitors MeSH
- Cobalt MeSH
- Hydroxyeicosatetraenoic Acids MeSH
- Oxygenases MeSH
- Renin MeSH
- Cytochrome P-450 Enzyme System MeSH
- Triazoles MeSH
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.
References provided by Crossref.org
Research on Experimental Hypertension in Prague (1966-2009)
