Beneficial renal effects of CS-905, a novel dihydropyridine calcium blocker, in SHR.
CS-905 is a potent dihydropyridine calcium blocker that has a gradual and long-lasting antihypertensive action with little tachycardia in SHR. In this study, we investigated chronic and acute effects of CS-905 on renal functions in SHR. To examine the chronic effects, 23 week-old male SHR were treated with CS-905 (1 or 3 mg/kg/day, p.o.) or 0.3% CMC (carboxymethylcellulose). After the 15 week-treatment, the agent dose-relatedly lowered systolic blood pressure measured 24 hr after the final administration (184 +/- 2 and 173 +/- 3 mmHg at 1 and 3 mg/kg/day vs. 218 +/- 4 mmHg for the control group). Natriuresis and the reduction of urinary protein excretion were also observed in the CS-905 treated groups. Urinary NAG (N-acetyl-beta-D-glucosaminidase) activity tended to decrease, but not significantly. Histopathological changes observed in the SHR kidney were reduced by chronic treatment with CS-905. On a single oral administration in 38 week-old SHR, CS-905 caused natriuresis at a dose of 3 mg/kg, but did not affect urinary protein excretion and urinary NAG activity. These effects of CS-905 on renal functions may be beneficial in the treatment of hypertension.
Oizumi
K
K
Sankyo Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Nishino
H
H
Miyamoto
M
M
Fukushige
J
J
Fukami
M
M
Koike
H
H
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001385:Azetines; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; D000118:Acetylglucosaminidase; C061679:azelnidipine