Related Experiment Videos
Intraglomerular expression of alpha-smooth muscle actin in aging mice
L A Romano1, L Ferder, F Inserra
1Hospital Israelita, Buenos Aires, Argentina.
Abstract:
To determine whether chronic treatment with enalapril initiated early in life prevents glomerular injury secondary to normal aging, CF1 mice received enalapril (20 mg/L, n = 10) or nifedipine (40 mg/L, n = 10) in their drinking water from the time of weaning to 12 months of life. Control mice (n = 10) received tap water ad libitum. Immunocytochemical detection of renin confirmed that angiotensin-converting enzyme inhibition resulted in recruitment of renin-containing cells along the preglomerular vessels. Morphometric analysis of glomeruli included assessment of glomerular diameter and the percentage of mesangial area per glomerulus. Glomerular diameter and mesangial area were higher in control mice (99.7 +/- 0.5 microns, 12.7 +/- 0.3%) than in enalapril-treated mice (88 +/- 0.8 microns, 8.6 +/- 0.6%) (P < .05). Glomerular diameter and mesangial area in the nifedipine-treated group (99.1 +/- 0.9 microns, 12.4 +/- 0.9%) were not different from control mice. These results demonstrate that angiotensin-converting enzyme inhibition prevents the glomerular enlargement and mesangial expansion observed during natural aging. In addition, control glomeruli expressed alpha-smooth muscle actin in a mesangial distribution. This effect was prevented by enalapril treatment but not by nifedipine. We conclude that long-term treatment with enalapril from early life prevents the early changes associated with glomerular injury and expression of alpha-smooth muscle actin in the glomerulus. alpha-Smooth muscle actin may participate in and serve as an early marker of the glomerular injury during the normal aging process.
Insights
Early enalapril treatment prevents age-related kidney damage in mice by inhibiting angiotensin-converting enzyme. This intervention reduces glomerular enlargement and mesangial expansion, suggesting a protective role against aging-induced kidney injury.
Area of Science:
- Nephrology
- Gerontology
- Pharmacology
Background:
- Aging is associated with progressive glomerular injury, including enlargement and mesangial expansion.
- Alpha-smooth muscle actin expression in glomeruli may indicate early stages of injury during aging.
Purpose of the Study:
- To investigate if early-life, chronic enalapril treatment can prevent age-related glomerular injury in mice.
- To assess the impact of enalapril on glomerular morphology and alpha-smooth muscle actin expression during aging.
Main Methods:
- CF1 mice received enalapril or nifedipine in drinking water from weaning to 12 months.
- Control mice received tap water.
- Immunocytochemistry for renin and morphometric analysis of glomeruli (diameter, mesangial area) were performed.
- Alpha-smooth muscle actin expression was evaluated.
Main Results:
- Enalapril treatment significantly reduced glomerular diameter and mesangial area compared to controls (P < .05).
- Nifedipine treatment did not alter glomerular diameter or mesangial area.
- Enalapril prevented the age-associated increase in alpha-smooth muscle actin expression in glomeruli.
Conclusions:
- Chronic angiotensin-converting enzyme inhibition with enalapril, initiated early in life, effectively prevents glomerular enlargement and mesangial expansion during aging.
- Enalapril mitigates early glomerular injury markers, including alpha-smooth muscle actin expression.
- Alpha-smooth muscle actin may serve as an early indicator of glomerular injury in the aging process.