Enalapril and losartan attenuate mitochondrial dysfunction in aged rats

FASEB J. 2003 Jun;17(9):1096-8. doi: 10.1096/fj.02-0063fje. Epub 2003 Apr 22.


Renin-angiotensin system (RAS) inhibition can attenuate the effects of aging on renal function and structure; however, its effect on mitochondrial aging is unknown. To investigate whether an angiotensin-converting enzyme inhibitor (enalapril) or an angiotensin II receptor blocker (losartan) could mitigate age-associated changes in kidney mitochondria, male Wistar rats (14 mo old) received during 8 mo water containing either enalapril (10 mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no additions (Old). Four-month-old untreated rats (Young) were also studied. In Old rats mitochondrial respiratory control, ADP/O, nitric oxide synthase activity, and uncoupling protein 2 levels were lower (46, 42, 27, and 76%, respectively), and Mn-SOD activity was higher (70%) than in Young, Enal, and Los rats. In Old rats mitochondrial hydrogen peroxide production was higher than in both Young (197%) and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was lower than in both Young (80%) and Enal (57%) or Los (68%) rats. In Old rats electron microscopy showed effacement of microvilli in tubular epithelial cells, ill-defined mitochondrial cristae, lower mitochondrial numbers, and enhanced number of osmiophilic bodies relative to Young, Enal, or Los rats. In conclusion, enalapril and losartan can protect against both age-related mitochondrial dysfunction and ultrastructural alterations, underscoring the role of RAS in the aging process. An association with oxidative stress modulation is suggested.

MeSH terms

  • Aging*
  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Cell Respiration
  • Enalapril / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / ultrastructure
  • Glutathione / metabolism
  • Kidney / metabolism
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / ultrastructure
  • Losartan / pharmacology*
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Mitochondria / ultrastructure
  • Models, Biological
  • Oxidation-Reduction
  • Rats
  • Rats, Wistar


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Enalapril
  • Glutathione
  • Losartan