Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
Curr Hypertens Rev. 2013 May;9(2):108-14. doi: 10.2174/15734021113099990005.
The renoprotective effects of benidipine, a calcium channel blocker (CCB) developed in Japan, are reviewed herein. Benidipine has a sustained antihypertensive effect independent of its blood concentration since it binds to dihydropyridine (DHP) receptors via a "membrane approach" (approach to the cell membrane followed by long retention at the DHP binding site). Benidipine dilates glomerular afferent and efferent arterioles equally through inhibition of Ttype Ca channels. Thus, it may cause a decrease of intraglomerular pressure and is superior to CCBs (capable of inhibiting only L-type Ca channels) in terms of suppression of proteinuria. Additionally, benidipine suppresses worsening of renal function more powerfully than CCBs (suppressing only L-type Ca channels), allowing better prognosis as to renal function. The inhibitory effect of benidipine on T-type calcium channels results in the suppression of aldosterone formation in the adrenal glands and of oxidative stress induced by aldosterone. Thus, the aldosterone-inhibitory and antioxidant activities of benidipine mediated by inhibition of T-type calcium channels would result in renoprotection and suppression of disease progression in hypertensive patients with chronic kidney disease (CKD). If such patients have proteinuria, renin-angiotensin system (RAS) inhibitors are used as first-line drugs, but benidipine, as an L-/T-type CCB, is recommended when they require some concomitant drugs. Moreover, the superiority of RAS inhibitors has not been demonstrated in hypertensive patients with CKD and without proteinuria. Thus, in such patients, benidipine should be considered as a first-line antihypertensive drug.
本文综述了日本研发的钙通道阻滞剂（CCB）贝尼地平的肾脏保护作用。贝尼地平通过“膜途径”（作用于细胞膜并长时间滞留在二氢吡啶（DHP）结合位点）与DHP受体结合，具有不依赖于血药浓度的持续降压作用。贝尼地平通过抑制T型钙通道，同等程度地扩张肾小球入球小动脉和出球小动脉。因此，它可能导致肾小球内压降低，在抑制蛋白尿方面优于仅能抑制L型钙通道的CCB。此外，贝尼地平比仅抑制L型钙通道的CCB更有效地抑制肾功能恶化，从而使肾功能预后更好。贝尼地平对T型钙通道的抑制作用导致肾上腺醛固酮生成减少以及醛固酮诱导的氧化应激受到抑制。因此，贝尼地平通过抑制T型钙通道介导的醛固酮抑制和抗氧化活性可实现肾脏保护，并抑制慢性肾脏病（CKD）高血压患者的疾病进展。如果此类患者有蛋白尿，肾素-血管紧张素系统（RAS）抑制剂用作一线药物，但当他们需要一些联合用药时，推荐使用作为L-/T型CCB的贝尼地平。此外，RAS抑制剂在无蛋白尿的CKD高血压患者中的优势尚未得到证实。因此，在此类患者中，贝尼地平应被视为一线降压药物。
