Enalapril and losartan attenuate mitochondrial dysfunction in aged rats.
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.
de Cavanagh
Elena M V
EM
Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Piotrkowski
Barbara
B
Basso
Nidia
N
Stella
Ines
I
Inserra
Felipe
F
Ferder
Leon
L
Fraga
Cesar G
CG
D000375:Aging; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019069:Cell Respiration; D004656:Enalapril / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000648:ultrastructure; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008954:Models, Biological; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D005978:Glutathione; D019808:Losartan