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Published on: August 22, 2014
Enalapril and losartan attenuate mitochondrial dysfunction in aged rats
Elena M V de Cavanagh1, Barbara Piotrkowski, Nidia Basso
1Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Summary
Renin-angiotensin system inhibitors like enalapril and losartan protect aging kidneys from mitochondrial damage and structural changes. These drugs mitigate age-related declines in kidney function and oxidative stress.
Area of Science:
- Gerontology
- Nephrology
- Mitochondrial Biology
Background:
- Aging negatively impacts renal function and structure.
- Renin-angiotensin system (RAS) inhibition shows protective effects against aging's renal effects.
- The impact of RAS inhibition on mitochondrial aging remains unclear.
Purpose of the Study:
- To investigate if ACE inhibitor (enalapril) or ARB (losartan) mitigate age-associated kidney mitochondrial changes.
- To assess the effects of RAS inhibition on mitochondrial function and structure in aging rats.
Main Methods:
- Male Wistar rats (14 months old) were treated for 8 months with enalapril, losartan, or water (Old group).
- A young (4-month-old) untreated group (Young) served as a control.
- Mitochondrial function (respiratory control, ADP/O, enzyme activities, oxidative stress markers) and kidney ultrastructure were analyzed.
Main Results:
- Aging rats (Old) exhibited reduced mitochondrial respiratory control, ADP/O, nitric oxide synthase activity, and uncoupling protein 2 levels.
- Old rats showed increased Mn-SOD activity and hydrogen peroxide production, and decreased GSH/GSSG ratio compared to Young, Enal, and Los groups.
- Electron microscopy revealed microvilli effacement, poor mitochondrial cristae definition, and fewer mitochondria in Old rats.
Conclusions:
- Enalapril and losartan protect against age-related mitochondrial dysfunction and kidney ultrastructural damage.
- RAS plays a significant role in the aging process of kidney mitochondria.
- RAS inhibition's protective effects may involve modulation of oxidative stress.
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