Comparison between YM099 and captopril in rats with renal mass reduction-induced progressive renal disease.
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.
Yatsu
Takeyuki
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yatsu@yamanouchi.co.jp
Aoki
Motonori
M
Uchida
Wataru
W
Inagaki
Osamu
O
D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D010069:Oxadiazoles / Q000627:therapeutic use*; D015221:Potassium Channels / Q000502:physiology; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D003497:Cyclic N-Oxides; D010069:Oxadiazoles; D015221:Potassium Channels; C091804:YM 099; D002216:Captopril