Effect of a Specific Endothelin Receptor A Antagonist on Glomerulonephritis of ddY Mice with IgA Nephropathy

Abstract

The present study assessed renal endothelin (ET)-l 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, FR139317, 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 mtraperitoneally 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.