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Renin‐angiotensin system (RAS) inhibition (i) attenuates the decrease in age related mitochondrial (mt) DNA content
Author(s) -
Cavanagh Elena MV,
Inserra Felipe,
Flores Idhaliz,
Maldonado Manuel Martinez,
Ferder Leon Fernando
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1160
Subject(s) - losartan , mitochondrial dna , medicine , endocrinology , chemistry , weaning , microbiology and biotechnology , renin–angiotensin system , angiotensin ii , biology , biochemistry , blood pressure , gene
RASi ameliorates age‐related mt dysfunction and increases rodent lifespan. We studied if mt protection by RASi is related to mtDNA “common deletion” (mtDNA 4834 ) level changes. Wistar rats (n=6 rats/group) were given water with Enalapril (10 mg/kg.day, E), or Losartan (30 mg/kg.day, L), or plain water (A), from weaning up to 22 mo old. 4‐mo old rats were young controls (Y). Livers were used for DNA and mt isolation. Frequency of mtDNA 4834 and mtDNA/nuclear (n) DNA ratio (mtDNA copy number) were determined by real time PCR (SYBRGreen). H 2 O 2 production (fluorometry), O 2 consumption (O 2 electrode), MnSOD (spectrophotometry) and NOS activity ( 14 C‐Arg to 14 C‐citrulline)were determined in mt. mtDNA 4834 frequency was similar among groups. Differences were in: a) mtDNA/nDNA, 1.15±0.16 (A), 1.61±0.05 ¬* (E), 1.62±0.04 ¬* (L), 3.2±0.06*(Y); b) H 2 O 2 (nmol/min.mg protein (p)) 9.42±0.91 (A), 6.76±0.93* (E), 6.34±0.88* (L), 2.99±0.58* (Y); c) MnSOD (U/mg p), 64.1±0.20 (A), 35.4±0.21* (E), 33.6±0.43* (L), 30.9±0.27* (Y); d) ADP/O, 1.75±0.22 (A), 2.79±0.41* (E); 3.23±0.30* (L), 3.01±0.54* (Y); e) mtNOS (nmol citrulline/min.mg p), 0.69±0.04 (A), 1.01±0.07* (E), 1.21±0.43* (L), 1.05±0.11* (Y), (¬p<0.05 vs Y, * p<0.05 vs A). Since mtDNA encodes for 13 polypeptides of mt electron transport chain, the attenuation of age‐associated mtDNA level lowering by RASi may underlie mt function amelioration.