PMID- 21270815
OWN - NLM
STAT- MEDLINE
DCOM- 20110901
LR  - 20151119
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Linking)
VI  - 34
IP  - 4
DP  - 2011 Apr
TI  - L/N-type calcium channel blocker cilnidipine ameliorates proteinuria and inhibits 
      the renal renin-angiotensin-aldosterone system in deoxycorticosterone 
      acetate-salt hypertensive rats.
PG  - 521-9
LID - 10.1038/hr.2010.279 [doi]
AB  - Cilnidipine, an N/L-type calcium channel blocker, has been reported to inhibit 
      sympathetic nerve activity and has a greater renoprotective effect than L-type 
      calcium channel blockers. To investigate the hypothesis that cilnidipine might 
      ameliorate advanced hypertensive nephropathy and inhibit the renal 
      renin-angiotensin-aldosterone system, cilnidipine (1 mg per kg per day) or 
      amlodipine (1 mg per kg per day) was administered to uninephrectomized 
      deoxycorticosterone (DOCA)-salt hypertensive rats (DOCA-salt) for 4 weeks by 
      gavage. Although the blood pressure in the DOCA-salt group was higher than that 
      of control, neither cilnidipine nor amlodipine had any effect on the increase in 
      blood pressure in the DOCA-salt group. The DOCA (40 mg per kg per week, 
      subcutaneously (s.c.)) and salt (1% NaCl in drinking water) treatment 
      significantly aggravated the levels of urinary protein excretion and creatinine 
      clearance and increased glomerulosclerosis and collagen deposition in the 
      tubulointerstitial area of the kidney. These effects were attenuated by 
      cilnidipine treatment. Reverse transcription-polymerase chain reaction analysis 
      revealed that the renal expression of mRNA for collagen I/IV and transforming 
      growth factor-beta was enhanced in the DOCA-salt group and that the overexpression 
      of these molecules was suppressed by cilnidipine. Nicotinamide adenine 
      dinucleotide phosphate (NADPH) oxidase-derived superoxide production in the 
      kidney and urinary norepinephrine excretion, which were enhanced in the DOCA-salt 
      group, were suppressed by cilnidipine. Cilnidipine also decreased the activity 
      and expression of angiotensin-converting enzyme (ACE) and the aldosterone 
      concentration in the renal homogenate. Although neither cilnidipine nor 
      amlodipine had any effect on the increased blood pressure in the DOCA-salt group, 
      these renal changes were not induced by treatment with amlodipine. In conclusion, 
      cilnidipine inhibited renal dysfunction, sympathetic nerve activity and renal 
      renin-angiotensin-aldosterone system in the DOCA-salt group.
FAU - Toba, Hiroe
AU  - Toba H
AD  - Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto 
      Pharmaceutical University, Kyoto, Japan. toba@mb.kyoto-phu.ac.jp
FAU - Yoshida, Mamiko
AU  - Yoshida M
FAU - Tojo, Chisato
AU  - Tojo C
FAU - Nakano, Arisa
AU  - Nakano A
FAU - Oshima, Yuko
AU  - Oshima Y
FAU - Kojima, Yushi
AU  - Kojima Y
FAU - Noda, Kazuki
AU  - Noda K
FAU - Wang, Jiahong
AU  - Wang J
FAU - Kobara, Miyuki
AU  - Kobara M
FAU - Nakata, Tetsuo
AU  - Nakata T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20110127
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Calcium Channels, N-Type)
RN  - 0 (Dihydropyridines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NPHS2 protein)
RN  - 0 (Transforming Growth Factor beta)
RN  - 1J444QC288 (Amlodipine)
RN  - 40GP35YQ49 (Desoxycorticosterone)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - 9007-34-5 (Collagen)
RN  - 97T5AZ1JIP (cilnidipine)
SB  - IM
MH  - Amlodipine/pharmacology/therapeutic use
MH  - Animals
MH  - Calcium Channel Blockers/*pharmacology/*therapeutic use
MH  - Calcium Channels, L-Type/drug effects
MH  - Calcium Channels, N-Type/drug effects
MH  - Collagen/metabolism
MH  - Desoxycorticosterone/adverse effects
MH  - Dihydropyridines/*pharmacology/*therapeutic use
MH  - Disease Models, Animal
MH  - Hypertension/chemically induced/*drug therapy/physiopathology
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Kidney/drug effects/metabolism/pathology
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Proteinuria/*prevention & control
MH  - Rats
MH  - Rats, Wistar
MH  - Renin-Angiotensin System/*drug effects/physiology
MH  - Sodium Chloride/adverse effects
MH  - Transforming Growth Factor beta/metabolism
MH  - Treatment Outcome
EDAT- 2011/01/29 06:00
MHDA- 2011/09/02 06:00
CRDT- 2011/01/29 06:00
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2011/09/02 06:00 [medline]
AID - hr2010279 [pii]
AID - 10.1038/hr.2010.279 [doi]
PST - ppublish
SO  - Hypertens Res. 2011 Apr;34(4):521-9. doi: 10.1038/hr.2010.279. Epub 2011 Jan 27.