Homma Koichiro, Hayashi Koichi, Yamaguchi Shintaro, Fujishima Seitaro, Hori Shingo, Itoh Hiroshi
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Curr Hypertens Rev. 2013 Aug;9(3):182-6. doi: 10.2174/1573402110666140131160617.
It has recently been reported that voltage-dependent Ca channel subtypes, e.g., L-, T-, N-, and P/Q-type, are expressed in renal arterioles and renal tubules, and the inhibition of these channels exerts various effects on renal microcirculation. For example, selective blockade of L-type Ca channels with nifedipine preferentially dilates the afferent arteriole and potentially induces glomerular hypertension. On the other hand, recently developed Ca channel blockers (CCBs) such as mibefradil and efonidipine block both T-type and L-type Ca channels and consequently dilate both afferent and efferent arterioles, leading to lowering of intraglomerular pressure. Interestingly, aldosterone has recently been recognized as a factor exacerbating renal diseases, and its secretion from adrenal gland is mediated by T-type Ca channels. Furthermore, T-type CCBs were shown to ameliorate renal dysfunction by suppressing inflammatory processes and renin secretion. On the basis of histological evaluations, N-type Ca channels are present in peripheral nerve terminals innervating both afferent and efferent arterioles. Further, it was suggested that N-type CCBs such as cilnidipine suppress renal arteriolar constriction induced by enhanced sympathetic nerve activity, thereby lowering intraglomerular pressure. Taken together, various Ca channel subtypes are present in the kidney and blockade of selective channels with distinct CCBs exerts diverse effects on renal microcirculation. Inhibition of T-type and N-type Ca channels with CCBs is anticipated to exert pleiotropic effects that would retard the progression of chronic kidney disease through modulation of renal hemodynamic and non-hemodynamic processes.
最近有报道称，电压依赖性钙通道亚型，如L型、T型、N型和P/Q型，在肾小动脉和肾小管中表达，抑制这些通道会对肾微循环产生多种影响。例如，用硝苯地平选择性阻断L型钙通道会优先扩张入球小动脉，并可能诱发肾小球高血压。另一方面，最近开发的钙通道阻滞剂（CCB），如米贝拉地尔和依福地平，可同时阻断T型和L型钙通道，从而扩张入球和出球小动脉，导致肾小球内压降低。有趣的是，醛固酮最近被认为是加重肾脏疾病的一个因素，其从肾上腺的分泌由T型钙通道介导。此外，T型CCB被证明可通过抑制炎症过程和肾素分泌来改善肾功能障碍。基于组织学评估，N型钙通道存在于支配入球和出球小动脉的外周神经末梢中。此外，有人提出，西尼地平之类的N型CCB可抑制交感神经活动增强引起的肾小动脉收缩，从而降低肾小球内压。综上所述，肾脏中存在多种钙通道亚型，用不同的CCB选择性阻断通道会对肾微循环产生不同的影响。预计用CCB抑制T型和N型钙通道会产生多效性作用，通过调节肾脏血流动力学和非血流动力学过程来延缓慢性肾脏病的进展。
