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

• Main Authors: Bai Lei, Daisuke Nakano, Yoshihide Fujisawa, Ya Liu, Hirofumi Hitomi, Hiroyuki Kobori, Hirohito Mori, Tsutomu Masaki, Katsuhiko Asanuma, Yasuhiko Tomino, Akira Nishiyama
• Format: Article
• Language: English
• Published: Elsevier 2012-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319304803

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. Keywords:: cilnidipine, hypertension, N-type calcium channel, podocyte, renal sympathetic nerve