Renin-angiotensin system inhibitors protect against age-related changes in rat liver mitochondrial DNA content and gene expression.

ABSTRACT: Chronic renin-angiotensin system inhibition protects against liver fibrosis, ameliorates age-associated mitochondrial dysfunction and increases rodent lifespan. We hypothesized that life-long angiotensin-II-mediated stimulation of oxidant generation might participate in mitochondrial DNA "common deletion" formation, and the resulting impairment of bioenergetic capacity. Enalapril (10 mg/kg/d) or losartan (30 mg/kg/d) administered during 16.5 months were unable to prevent the age-dependent accumulation of rat liver mitochondrial DNA "common deletion", but attenuated the decrease of mitochondrial DNA content. This evidence - together with the enhancement of NRF-1 and PGC-1 mRNA contents - seems to explain why enalapril and losartan improved mitochondrial functioning and lowered oxidant produ

SUBMITTER: de Cavanagh EM 

PROVIDER: S-EPMC4871262 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature