title: Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte.
abstract: OBJECTIVE
  Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism.
  
  
  RESULTS
  SHR/ND were treated with vehicle (nU10), cilnidipine [33 mg/kg per day, orally (p.o.); nU11] or amlodipine (20 mg/kg per day, p.o.; nU9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters.
  
  
  CONCLUSIONS
  These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND.
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Fan
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohsaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Diah
authors.initials: D
authors.lastname: Suwarni
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noma
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D003404:Creatinine / Q000097:blood / Q000652:urine; D017931:DNA Primers / Q000235:genetics; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D017931:DNA Primers; D004095:Dihydropyridines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014280:Triglycerides; D017311:Amlodipine; C065927:cilnidipine; D003404:Creatinine
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