Jl. Simons et al., PATHOGENESIS OF GLOMERULAR INJURY IN THE FAWN-HOODED RAT - EARLY GLOMERULAR CAPILLARY HYPERTENSION PREDICTS GLOMERULAR SCLEROSIS, Journal of the American Society of Nephrology, 3(11), 1993, pp. 1775-1782
Fawn-hooded rats spontaneously develop focal and segmental glomerular
sclerosis, systemic hypertension, and proteinuria at a young age. Micr
opuncture and morphological studies were performed in two inbred strai
ns of fawn-hooded rats, FHH and FHL, with different susceptibilities t
o develop chronic renal failure. FHH rats have higher values for systo
lic blood pressure and proteinuria and more rapid development of focal
and segmental glomerular sclerosis and subsequent chronic renal failu
re as compared with genetically closely related FHL rats. FHH and FHL
strains and a Wistar control strain, WAG, were matched for age and wer
e studied at 16 wk. FHH, FHL, and WAG-old (WAG-0) strains were matched
for weight, and the last group was studied at 22 wk. WAG were also ma
tched for weight to a young group of FHH rats (FHH-Y), and these were
studied at 8 wk. In comparison with WAG and WAG-0 rats, FHH and FHH-Y
rats exhibited an increase in mean glomerular capillary hydraulic pres
sure (WAG, 52 +/- 1 mm Hg; WAG-0, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg;
FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermedia
te (56 +/- 2 mm Hg). No significant differences in glomerular volume w
ere found among groups. Moderate focal and segmental glomerular sclero
sis developed in FHH and FHH-Y rats, with values for older FHH rats be
ing significantly greater than those for WAG, WAG-0, and FHL animals.
Thus, the genetically determined sensitivity to develop proteinuria, f
ocal and segmental glomerular sclerosis, and chronic renal failure in
fawn-hooded rats correlated with early evidence of glomerular capillar
y hypertension. By contrast, glomerular hypertrophy was not associated
with and was not a prerequisite for early glomerular injury in fawn-h
ooded rats.