Renal protective effect of efonidipine hydrochloride (NZ-105), a new calcium antagonist, in spontaneously hypertensive rats.
1. We investigated the renal protective effect of efonidipine hydrochloride (NZ-105) in spontaneously hypertensive rats (SHR). SHR were given a diet containing 0.075% NZ-105 from 8 weeks old for 20 weeks. 2. 24-hr urinary protein excretion in the control SHR (drug-free diet) increased with age (from 77.3 mg/kg/day at 8 weeks old to 385.4 mg/kg/day at 28 weeks old), while that in NZ-105-treated SHR was maintained at almost the same level as that in Wistar-Kyoto rats (WKY), matched control animals throughout the experimental period. 3. The histological changes of the kidney were examined by light microscopy at the end of the treatment period. In control SHR, swelling and hyalinization of glomeruli, dilatation of renal tubules containing hyaline casts and arteriolosclerosis were revealed. The long-term administration of NZ-105 markedly suppressed these changes. 4. The kidney weights and plasma creatinine concentration in control SHR were higher than those in WKY, while they were significantly reduced in NZ-105-treated SHR. The long-term administration of NZ-105 also suppressed the elevation of systolic blood pressure and the increases of plasma renin activity and aldosterone concentration. 5. These findings suggest that NZ-105 inhibits the development of proteinuria and progressive kidney damage in SHR and may become a useful antihypertensive drug with the renal protective effect.
Shudo
C
C
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Masuda
Y
Y
Sugita
H
H
Furukawa
S
S
Hayashi
K
K
Hirata
H
H
Tanaka
S
S
Tomita
K
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009596:Nitrophenols; D009929:Organ Size; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011507:Proteinuria; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine