The present study assessed renal
endothelin (ET)-1, ET-3, and ET receptor A and B
mRNA levels in ddY mice at 8, 40, and 60 weeks of age. The renal
mRNA levels of ET-1 increased significantly in ddY mice as their
nephritis progressed, reaching a 6.6-fold (p < 0.01) higher level by 60 weeks than in control ICR mice. Renal ET-3
mRNA levels, however, remained unchanged. The renal
mRNA levels of ET receptor A and B in ddY mice increased gradually with the progression of
nephritis, reaching 4.8- (p < 0.01) and 3.6-fold (p < 0.01) higher levels, respectively, at 60 weeks of age than found in control ICR mice. A positive correlation was noted between ET-1 and ET receptor
mRNA levels and histopathological changes in renal tissues. In addition, we assessed whether a specific ET receptor A antagonist,
FR 139317, affects the progression of
glomerulonephritis in ddY mice. At 24 weeks of age (before
glomerulonephritis developed), ddY mice were divided into two groups that received intraperitoneally either
FR139317 or its vehicle (saline) daily for 36 weeks. The development of histopathological lesions and urinary
protein excretion were suppressed by
FR139317 treatment. These data suggest that ET families play a role in the progression of
glomerulonephritis and that
FR139317 treatment can be used therapeutically in ddY mice with
IgA nephropathy.