Effects of efonidipine, nicardipine and captopril on proteinuria in aged spontaneously hypertensive rats

Previous studies have shown that antihypertensive drugs attenuate the progression of proteinuria by their treatments from young age, but few have examined their effects on impaired renal function in older age. In the present study the calcium antagonists efonidipine ((+/-)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl -5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol, CAS 111011-76-8, NZ-105) and nicardipine, and an angiotensin-converting enzyme inhibitor, captopril, were examined for their effects on heavy proteinuria in aged spontaneously hypertensive rats (SHR). Efonidipine (20 mg/kg), nicardipine (20 mg/kg) and captopril (30 mg/kg) were orally administered once a day for 4 weeks. The urinary protein excretion (UproE) increased with age (54.9 mg/kg/day at 24 weeks of age to 170.8 mg/kg/day at 36 weeks). The increased UproE was significantly suppressed by daily administration of efonidipine or captopril as compared to that in the non drug treated control group. The UproE in the nicardipine group was maintained at a slightly lower level than in the control. The histological examination showed that the damages of the kidneys were slightly suppressed by efonidipine and captopril. These findings indicate that. efonidipine as well as captopril reduce proteinuria in aged SHR and the effect was stronger than that of nicardipine. This beneficial effect of efonidipine on proteinuria suggests its usefulness in antihypertensive therapy.