The effects of the
ATP-sensitive
potassium (
KATP) channel opener
YM099, and the
angiotensin-converting enzyme (
ACE) inhibitor captopril, on the progression of renal disease in rats with surgical renal mass reduction (RMR) were evaluated. Rats were subtotal (5/6) nephrectomized by resection of the renal poles. After 2 weeks of RMR, rats were randomized to three groups and treated for 6 weeks: no treatment (n=9);
YM099 at a dose of 0.3 mg/kg by daily
oral administration (n=9); or
captopril at a dose of 50 mg/kg by daily
oral administration (n=9).
Sham-operated rats were used as normal animals (n=9). In RMR rats with no treatment,
proteinuria progressively developed. At 8 weeks after RMR, renal function as assessed by plasma
creatinine (Pcr) and blood
urea nitrogen (BUN) was impaired. Pharmacological activation of
KATP channel opening by
YM099 showed no beneficial effect on
proteinuria and renal functional parameters. On the other hand, pharmacological ACE inhibition by
captopril significantly attenuated
proteinuria, and tended to inhibit the increases in Pcr and BUN; however, these effects were not statistically significant. The presents study indicates that
YM099 exhibits no renoprotection with antiproteinuric effect in rats with progressive renal disease. These findings suggest that activation of
KATP channel opening may play no role in the retardation of progressive renal disease.