Shudo C, Masuda Y, Sugita H, Tamura T, Furukawa S, Hayashi K, Hirata H, Shikada K, Tanaka S, Tomita K
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Arzneimittelforschung. 1996 Sep;46(9):852-4.
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-pyridinecarboxyla te 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.
以往研究表明，抗高血压药物从年轻时开始治疗可减轻蛋白尿进展，但很少有研究考察其对老年肾功能受损的影响。在本研究中，对钙拮抗剂依福地平（(+/-)-2-[苄基（苯基）氨基]乙基 1,4-二氢-2,6-二甲基-5-(5,5-二甲基-2-氧代-1,3,2-二氧磷杂环己烷-2-基)-4-(3-硝基苯基)-3-吡啶羧酸盐酸盐乙醇，CAS 111011-76-8，NZ-105）、尼卡地平和血管紧张素转换酶抑制剂卡托普利对老年自发性高血压大鼠（SHR）重度蛋白尿的影响进行了研究。依福地平（20 mg/kg）、尼卡地平（20 mg/kg）和卡托普利（30 mg/kg）每日口服给药1次，共4周。尿蛋白排泄量（UproE）随年龄增加而升高（24周龄时为54.9 mg/kg/天，36周龄时为170.8 mg/kg/天）。与未用药对照组相比，每日给予依福地平或卡托普利可显著抑制UproE的升高。尼卡地平组的UproE维持在略低于对照组的水平。组织学检查表明，依福地平和卡托普利可轻微抑制肾脏损伤。这些发现表明，依福地平和卡托普利均可降低老年SHR的蛋白尿，且效果强于尼卡地平。依福地平对蛋白尿的这种有益作用表明其在抗高血压治疗中具有应用价值。
