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Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte.

AbstractOBJECTIVES:
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.
METHODS AND 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.
CONCLUSION:
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.
AuthorsYu-Yan Fan, Masakazu Kohno, Daisuke Nakano, Hiroyuki Ohsaki, Hiroyuki Kobori, Diah Suwarni, Naro Ohashi, Hirofumi Hitomi, Katsuhiko Asanuma, Takahisa Noma, Yasuhiko Tomino, Toshiro Fujita, Akira Nishiyama
JournalJournal of hypertension (J Hypertens) Vol. 28 Issue 5 Pg. 1034-43 (May 2010) ISSN: 1473-5598 [Electronic] England
PMID20411599 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • DNA Primers
  • Dihydropyridines
  • RNA, Messenger
  • RNA, Small Interfering
  • Triglycerides
  • Amlodipine
  • cilnidipine
  • Creatinine
Topics
  • Amlodipine (pharmacology)
  • Animals
  • Base Sequence
  • Blood Glucose (metabolism)
  • Blood Pressure (drug effects)
  • Body Weight (drug effects)
  • Calcium Channel Blockers (pharmacology)
  • Calcium Channels, N-Type (drug effects, genetics, metabolism)
  • Creatinine (blood, urine)
  • DNA Primers (genetics)
  • Dihydropyridines (pharmacology)
  • Disease Models, Animal
  • Humans
  • Kidney (drug effects, metabolism, pathology)
  • Male
  • Metabolic Syndrome (drug therapy, genetics, metabolism, pathology)
  • Oxidative Stress (drug effects)
  • Podocytes (drug effects, metabolism, pathology)
  • Proteinuria (prevention & control)
  • RNA, Messenger (genetics, metabolism)
  • RNA, Small Interfering (genetics)
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Renin-Angiotensin System (drug effects)
  • Triglycerides (blood)

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