N-type calcium channel inhibition with cilnidipine elicits glomerular podocyte protection independent of sympathetic nerve inhibition

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. © the japanese pharmacological society.