title: N-type calcium channel inhibition with cilnidipine elicits glomerular podocyte protection independent of sympathetic nerve inhibition.
abstract: 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.
authors.affiliation: Department of Pharmacology, Kagawa University Medical School, Japan.
authors.forename: Bai
authors.initials: B
authors.lastname: Lei
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002460:Cell Line; D003893:Desmin / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D003893:Desmin; D004095:Dihydropyridines; D020011:Protective Agents; D000804:Angiotensin II; C065927:cilnidipine