Konno Yuusuke, Kimura Kenjiro
Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kanagawa, Japan.
Int Heart J. 2008 Nov;49(6):723-32. doi: 10.1536/ihj.49.723.
Cilnidipine is a dihydropyridine calcium channel blocker that acts on both L-type and N-type calcium channels. The effects of cilnidipine given intravenously at doses of 2.5, 5.0, and 10 microg/kg were studied using an ex vivo hydronephrosis model in spontaneously hypertensive rats. The effects of nifedipine at a dose of 10 microg/kg were also studied using the same model as a reference. Cilnidipine caused dose-dependent blood pressure reduction and dilatation of the glomerular afferent arterioles; the arteriolar diameter after cilnidipine infusion at 2.5, 5.0, and 10 microg/kg was 101% +/- 3%, 112% +/- 4%, and 123% +/- 6% relative to baseline, respectively. With cilnidipine, dilatation of the efferent arterioles was also observed; it was maximal after 5 to 10 minutes. Five minutes after administration of 2.5, 5.0, and 10 microg/kg of cilnidipine, the efferent arteriolar diameter was 103% +/- 2%, 109% +/- 4%, and 119% +/- 4% of baseline, respectively. This efferent arteriolar dilating action of cilnidipine was abolished after pretreatment with omega-conotoxin, a selective N-type calcium channel blocker. A dose-dependent increase of glomerular blood flow volume was also observed after cilnidipine infusion. Nifedipine, an L-type calcium channel blocker, at a dose of 10 microg/kg reduced systolic blood pressure to a similar extent as cilnidipine at a dose of 10 microg/kg, but only dilated the afferent arterioles and had no significant effect on efferent arterioles. Cilnidipine dilated both the afferent and efferent glomerular arterioles. The efferent arteriolar dilating effect of cilnidipine may be attributed to its inhibition of the N-type calcium channel.
西尼地平是一种二氢吡啶类钙通道阻滞剂，作用于L型和N型钙通道。在自发性高血压大鼠的离体肾积水模型中，研究了静脉注射2.5、5.0和10微克/千克剂量西尼地平的效果。还使用相同模型研究了10微克/千克剂量硝苯地平的效果作为对照。西尼地平引起剂量依赖性的血压降低和肾小球入球小动脉扩张；静脉注射2.5、5.0和10微克/千克西尼地平后，小动脉直径相对于基线分别为101%±3%、112%±4%和123%±6%。使用西尼地平时，也观察到出球小动脉扩张；在5至10分钟后达到最大。静脉注射2.5、5.0和10微克/千克西尼地平5分钟后，出球小动脉直径分别为基线的103%±2%、109%±4%和119%±4%。西尼地平的这种出球小动脉扩张作用在用选择性N型钙通道阻滞剂ω-芋螺毒素预处理后被消除。静脉注射西尼地平后还观察到肾小球血流量呈剂量依赖性增加。10微克/千克剂量的L型钙通道阻滞剂硝苯地平降低收缩压的程度与10微克/千克剂量的西尼地平相似，但仅扩张入球小动脉，对出球小动脉无显著影响。西尼地平使肾小球入球和出球小动脉均扩张。西尼地平的出球小动脉扩张作用可能归因于其对N型钙通道的抑制。
