Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 51, Issue 2 M80-M85, Copyright © 1996 by The Gerontological Society of America
Glomerular dysfunction in the aging Fischer 344 rat is associated with excessive growth and normal mesangial cell function
GF McDermott, A Ingram, J Scholey, JL Kirkland and CI Whiteside
M.R.C. Group in Membrane Biology, Division of Geriatrics, University of Toronto, Canada.
BACKGROUND: Fischer 344 (F344) rats display focal and diffuse
glomerulosclerosis with aging postulated to result from loss of normal
mesangial cell intrinsic function, e.g., vasoactive hormone signaling, or
preservation of normal responsiveness to extrinsic growth factors. METHODS:
In 3-, 17-, and 24-month-old F344 male rats, glomerular structure, measured
by PC-based morphometry, and function were compared. Immunoperoxidase
staining of glomerular proliferating cell nuclear antigen (PCNA) detected
cellular proliferation. Primary cultured mesangial cells from the 3 age
groups were studied in parallel. Calcium (Ca2+) signaling, measured by
Fura-2 fluorescence, contraction to vasopressin (AVP) 1 microM, measured by
videomicroscopy, and proliferative response to platelet-derived growth
factor-beta beta (PDGF) were compared. RESULTS: Proteinuria was 13 +/- 4,
38 +/- 17, and 110 +/- 35 mg/24 hours at 3, 17, and 24 months, respectively
(n = 5, mean +/- SE, p < .01, 3 vs 24 months), with no change in 24-hour
creatinine clearances. Glomerular volumes (n = 200/group) for 3, 17, and 24
months, respectively, were .30 +/- .01, .60 +/- .02, .74 +/- 0.2 x 10(6)
micron3 (p < .001, 3 months vs 17 months, and 17 vs 24 months).
Glomerular basement membrane (GBM) widths and fractional mesangial volumes
increased significantly with aging. Glomerular cell PCNA staining remained
positive at 24 months. Cultured mesangial cell Ca2+ signaling and
contraction to AVP were unchanged with aging. Proliferation to PDGF, which
was partially inhibited with verapamil, was similar at 3 and 24 months.
CONCLUSIONS: In the Fischer 344 rat, mesangial cell Ca2+ signaling,
contraction, and proliferation responsiveness are unchanged with aging.
Continued growth is associated with the glomerulosclerosis of aging.
