Effects of the antihypertensive drug nifedipine on albuminuria and renal histopathology in young spontaneously hypertensive rats with diabetes.
We investigated the renal protective effect of nifedipine (2-nitrophenyl derivative BAY a 1040) in streptozotocin (STZ)-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 40 mg/kg/day of nifedipine or efonidipine as controls for 16 weeks. Dosage of nifedipine or efonidipine was chosen after preliminary studies demonstrated that it showed moderate antihypertensive action (more than a 20% decrease in systemic blood pressure after treatment). In the diabetic SHR, the excretion of urinary albumin was increased and reached 4.41 +/- 0.08 mg/day at 24 weeks. The levels of urinary albumin in the diabetic SHR after treatment with nifedipine were significantly less than those in the diabetic SHR at 24 weeks (p < 0.01). Levels of the ratio of creatinine clearance to body weight were significantly decreased in the diabetic SHR after treatment with nifedipine. In light microscopy, the ratio of glomerular tufts to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (p < 0.05). These findings suggest that nifedipine inhibits the development of albuminuria and glomerular enlargement in STZ-induced diabetic SHRs. There was no significant difference in the changes in antihypertensive or antialbuminuric effects between nifedipine and efonidipine. Thus, nifedipine, as well as efonidipine, may become a useful antihypertensive drug with a renal protective effect.
Kaneko
S
S
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Takizawa
H
H
Takeda
M
M
Shou
I
I
Tomino
Y
Y
D000419:Albuminuria / Q000517:prevention & control*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003404:Creatinine / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000517:prevention & control*; D004095:Dihydropyridines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D014665:Vasodilator Agents; C066425:efonidipine; D003404:Creatinine; D009543:Nifedipine