Protective effect of benidipine against the development of glomerular sclerosis in experimental nephrotic syndrome.
An experimental focal segmental glomerular sclerosis (FSGS) was induced by the combined administration of puromycin aminonucleoside (PAN) and protamine sulfate (PS). Blood collections were made on days 0, 37, 70 and 94. Urine collections were made on days 0, 24, 80 and 94. Vehicle-treated rats showed severe proteinuria and an increase in serum total cholesterol (sTC). Benidipine (1 or 3 mg/kg, p.o.)-treated rats exhibited less proteinuria and lower sTC than the vehicle-treated rats. On days 70 and 94, both blood urea nitrogen (BUN) and serum creatinine (sCR) values in the vehicle-treated rats were significantly higher than those in normal rats (without treatment with PAN and PS). On the other hand, the treatment with benidipine (1 or 3 mg/kg, p.o.) attenuated the increases in BUN and sCR. On day 94, vehicle-treated rats showed a significant decrease in creatinine clearance as compared with normal rats, but benidipine (1 or 3 mg/kg, p.o.)-treated rats did not. The histology was examined on day 94. Vehicle-treated rats demonstrated a significantly greater percentage of glomeruli with segmental areas of glomerulosclerosis/hyalinosis, mesangial cell proliferation, and mesangial foam cell. Benidipine (3 mg/kg, p.o.) ameliorated the development of renal regeneration as estimated by histological examination. These results suggest that the Ca-channel blocker benidipine is a favorable drug for preventing the progression of glomerular sclerosis.
Shirakura
S
S
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Sano
J
J
Karasawa
A
A
Kubo
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000517:prevention & control* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000517:prevention & control* / Q000652:urine; D011479:Protamines; D011507:Proteinuria / Q000652:urine; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011479:Protamines; C061004:benidipine; D011692:Puromycin Aminonucleoside