N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

Journal of Pharmacological Sciences

Akira Nishiyama³  Hirofumi Hitomi³  Bai Lei³  Ya Liu³  Daisuke Nakano³  Tsutomu Masaki¹  Hiroyuki Kobori³  Yasuhiko Tomino²  Yoshihide Fujisawa³  Hirohito Mori¹  Katsuhiko Asanuma² 

[1] Department of Gastroenterology, Kagawa University Medical School, Japan;Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Japan;Department of Pharmacology, Kagawa University Medical School, Japan

关键词: cilnidipine;    hypertension;    N-type calcium channel;    podocyte;    renal sympathetic nerve;   

DOI  :  10.1254/jphs.12075FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(46)Cited-By(4)We recently demonstrated that cilnidipine, an L/N-type calcium channel blocker, elicits protective effects against glomerular podocyte injury, in particular, in obese hypertensive rats that express the N-type calcium channel (N-CC). Since the N-CC is known to be expressed in sympathetic nerve endings, we evaluated the reno-protective effects of cilnidipine in innervated and denervated spontaneously hypertensive rats (SHR). Male SHR were uninephrectomized and fed 4% high-salt diet (HS-UNX-SHR). Animals were divided into groups, as follows, and observed from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; n = 10), and 4) cilnidipine plus renal-denervation (n = 15). Renal denervation attenuated elevations in blood pressure, but failed to suppress urinary protein excretion and podocyte injury in HS-UNX-SHR. Cilnidipine in both innervated and denervated HS-UNX-SHR similarly induced significant antihypertensive effects, as well as suppressing the urinary protein excretion and podocyte injury, compared to vehicle-treated HS-UNX-SHR. These data indicate that renal nerves have a limited contribution to the cilnidipine-induced reno-protective effects in HS-UNX-SHR.

【 授权许可】

Unknown