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N型和L型钙通道阻滞剂西尼地平可抑制喂食高盐饮食的 Dahl 大鼠的肾损伤。

The N-type and L-type calcium channel blocker cilnidipine suppresses renal injury in Dahl rats fed a high-salt diet.

作者信息

Aritomi Shizuka, Koganei Hajime, Wagatsuma Hirotaka, Mitsui Akira, Ogawa Tetsuya, Nitta Kosaku, Konda Tomoyuki

机构信息

Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan.

出版信息

Heart Vessels. 2010 Nov;25(6):549-55. doi: 10.1007/s00380-010-0005-4. Epub 2010 Oct 5.

Abstract

The aims of the present study were to compare the effects of cilnidipine [L-type/N-type calcium channel blocker (CCB)] and amlodipine (L-type CCB) alone or in combination with the angiotensin II receptor blocker (ARB), valsartan, on blood pressure (BP), kidney function in Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet were divided into six groups; control (n = 13), two CCB (cilnidipine or amlodipine) groups at 1 mg/kg/day (n = 10), ARB (valsartan) at 10 mg/kg/day (n = 12), cilnidipine + valsartan (CV, n = 12), and amlodipine + valsartan (AV, n = 12). BPs were lower in the combination therapy groups than in those given either drug alone, but only CV inhibited the increase in urinary albumin excretion (UAE) and lowered the glomerular sclerosis score. In addition, AV elevated plasma renin activity and the angiotensin II concentration, and thus failed to inhibit increases in UAE and to lower glomerular sclerosis score. In conclusion, combination therapy with CCB and ARB decreases BP more effectively than either drug alone. When used in combination with valsartan, cilnidipine is more effective than amlodipine for preventing kidney injury.

摘要

本研究的目的是比较西尼地平[L型/N型钙通道阻滞剂(CCB)]和氨氯地平(L型CCB)单独使用或与血管紧张素II受体阻滞剂(ARB)缬沙坦联合使用对Dahl盐敏感(DS)大鼠血压(BP)、肾功能的影响。喂食高盐饮食的DS大鼠被分为六组:对照组(n = 13)、两个CCB组(西尼地平或氨氯地平,剂量为1 mg/kg/天,n = 10)、ARB组(缬沙坦,剂量为10 mg/kg/天,n = 12)、西尼地平+缬沙坦组(CV,n = 12)以及氨氯地平+缬沙坦组(AV,n = 12)。联合治疗组的血压低于单独使用任一药物的组,但只有CV抑制了尿白蛋白排泄(UAE)的增加并降低了肾小球硬化评分。此外,AV升高了血浆肾素活性和血管紧张素II浓度,因此未能抑制UAE的增加和降低肾小球硬化评分。总之,CCB与ARB联合治疗比单独使用任一药物更有效地降低血压。与缬沙坦联合使用时,西尼地平在预防肾损伤方面比氨氯地平更有效。

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