Ando Katsuyuki
Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3- 1 Hongo, Bunkkyo-ku, Tokyo, 113-8655, Japan.
Curr Hypertens Rev. 2013 Aug;9(3):210-8. doi: 10.2174/1573402110666140131155331.
The first-line depressor agents for hypertensive patients with chronic kidney disease are the renin-angiotensin system inhibitors because of their antiproteinuric and reno-protective effects. However, only one renin-angiotensin system inhibitor often cannot achieve target blood pressure in patients with injured kidney. Thus, second-line antihypertensives are required. Calcium channel blockers are frequently added on the renin-angiotensin system inhibitors in hypertensive patients with chronic kidney disease. However, they do not always show reno-protective effects because of their glomerular pressure-increasing action; Antihypetensive calcium channel blockers suppress L-type calcium channels, which exist in glomerular afferent but not efferent arterioles, and their afferent arteriole-specific vasodilation causes glomerular hypertension. The decrease in glomerular pressure due to their systemic hypotesive effect is counteracted by the glomerular pressure-incresing action. However, L-/N-type calcium channel blockers inhibits norepinephrine release from the sympathetic nerve terminal by blockade of N-type calcium channels, and dilate both afferent and efferent arterioles, which were innervated sympathetically, resulting in decrease in glomerular pressure. Actually, we have demonstrated that an L-/N-type calcium channel blocker cilnidipine decreased urinary protein more greatly than an L-type calcium channel blocker amlodipine in the renin-angiotensin system inhibitor-treated patients with chronic kidney disease. Thus, L-/N-type calcium channel blockers are one of suitable candidates for the second-line antihypertensives in the renin-angiotensin system inhibitor-treated hypertensive patients with proteinuria.
对于患有慢性肾病的高血压患者，一线降压药物是肾素-血管紧张素系统抑制剂，因为它们具有抗蛋白尿和肾脏保护作用。然而，在肾脏受损的患者中，仅使用一种肾素-血管紧张素系统抑制剂往往无法达到目标血压。因此，需要二线抗高血压药物。在患有慢性肾病的高血压患者中，常将钙通道阻滞剂添加到肾素-血管紧张素系统抑制剂上。然而，由于它们具有增加肾小球压力的作用，并不总是显示出肾脏保护作用；抗高血压钙通道阻滞剂抑制L型钙通道，该通道存在于肾小球入球小动脉而非出球小动脉中，其入球小动脉特异性血管舒张会导致肾小球高血压。由于其全身降压作用导致的肾小球压力降低被肾小球压力增加作用所抵消。然而，L-/N型钙通道阻滞剂通过阻断N型钙通道抑制去甲肾上腺素从交感神经末梢释放，并扩张受交感神经支配的入球和出球小动脉，从而导致肾小球压力降低。实际上，我们已经证明，在接受肾素-血管紧张素系统抑制剂治疗的慢性肾病患者中，L-/N型钙通道阻滞剂西尼地平比L型钙通道阻滞剂氨氯地平更能显著降低尿蛋白。因此，L-/N型钙通道阻滞剂是在接受肾素-血管紧张素系统抑制剂治疗的伴有蛋白尿的高血压患者中作为二线抗高血压药物的合适候选药物之一。
