PMID- 19633569
OWN - NLM
STAT- MEDLINE
DCOM- 20091123
LR  - 20191224
IS  - 1473-5598 (Electronic)
IS  - 0263-6352 (Linking)
VI  - 27
IP  - 9
DP  - 2009 Sep
TI  - Inhibitory effects of a dihydropyridine calcium channel blocker on renal injury 
      in aldosterone-infused rats.
PG  - 1855-62
LID - 10.1097/HJH.0b013e32832dda6f [doi]
AB  - OBJECTIVES: Recent in-vitro studies demonstrated that dihydropyridine calcium 
      channel blockers have direct mineralocorticoid receptor antagonistic activity. 
      The present study was conducted to examine the effects of a dihydropyridine 
      calcium channel blocker, azelnidipine, on aldosterone-induced oxidative stress 
      and renal injury. METHODS AND RESULTS: Uninephrectomized rats subjected to 6 
      weeks treatment with aldosterone (0.75 microg/h, subcutaneous) and 1% NaCl (in 
      drinking water) showed higher systolic blood pressure (SBP), urinary excretion of 
      protein (UproteinV), glomerular cell proliferation and renal interstitial 
      fibrosis than vehicle (2% ethanol)-infused rats. Aldosterone-induced renal injury 
      was associated with increased renal cortical content of thiobarbituric 
      acid-reactive substances (TBARS), NAD(P)H oxidase complex formation and mRNA 
      expression of NAD(P)H oxidase membrane components (p22 and gp91). Administration 
      of azelnidipine [3 mg/kg per day, orally (p.o.)] markedly attenuated the 
      aldosterone-induced increases in SBP, UproteinV, renal cortical tissues TBARS 
      content, NAD(P)H oxidase complex formation, mRNA levels of p22 and gp91, and 
      morphological changes. In aldosterone-infused rats, treatment with a nonspecific 
      vasodilator, hydralazine (5 mg/kg per day in drinking water) resulted in a 
      reduction in SBP similar to azelnidipine; however, it did not affect any renal 
      parameters. Treatment with azelnidipine suppressed aldosterone/mineralocorticoid 
      receptor-dependent but not mineralocorticoid receptor-independent superoxide 
      production in cultured rat mesangial cells. CONCLUSION: These data suggest that 
      dihydropyridine calcium channel blockers may elicit marked amelioration of 
      aldosterone-induced renal injury through their inhibitory effects on NAD(P)H 
      oxidase-dependent oxidative stress.
FAU - Fan, Yu-Yan
AU  - Fan YY
AD  - Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Japan.
FAU - Kohno, Masakazu
AU  - Kohno M
FAU - Nakano, Daisuke
AU  - Nakano D
FAU - Hitomi, Hirofumi
AU  - Hitomi H
FAU - Nagai, Yukiko
AU  - Nagai Y
FAU - Fujisawa, Yoshihide
AU  - Fujisawa Y
FAU - Lu, Xiao-Mei
AU  - Lu XM
FAU - Fu, Hua
AU  - Fu H
FAU - Du, Jun
AU  - Du J
FAU - Ohmori, Koji
AU  - Ohmori K
FAU - Hosomi, Naohisa
AU  - Hosomi N
FAU - Kimura, Shoji
AU  - Kimura S
FAU - Kiyomoto, Hideyasu
AU  - Kiyomoto H
FAU - Nishiyama, Akira
AU  - Nishiyama A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (CCN2 protein, rat)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Collagen Type IV)
RN  - 0 (Dihydropyridines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0 (Transforming Growth Factor beta)
RN  - 104821-25-2 (dihydroethidium)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - 4964P6T9RB (Aldosterone)
RN  - 5GZ3E0L9ZU (Azetidinecarboxylic Acid)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EN464416SI (Ethidium)
RN  - PV23P19YUG (azelnidipine)
SB  - IM
MH  - Aldosterone
MH  - Animals
MH  - Azetidinecarboxylic Acid/*analogs & derivatives/pharmacology/therapeutic use
MH  - Blood Pressure
MH  - Body Weight/drug effects
MH  - Calcium Channel Blockers/pharmacology/*therapeutic use
MH  - Collagen Type IV/metabolism
MH  - Connective Tissue Growth Factor/metabolism
MH  - Creatinine/blood/urine
MH  - Dihydropyridines/pharmacology/*therapeutic use
MH  - Ethidium/analogs & derivatives
MH  - Gene Expression
MH  - Kidney/pathology
MH  - Kidney Diseases/metabolism/pathology/*prevention & control
MH  - Male
MH  - Mesangial Cells/drug effects/metabolism
MH  - NADPH Oxidases/*antagonists & inhibitors/metabolism
MH  - Organ Size/drug effects
MH  - Proteinuria/urine
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2009/07/28 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/07/28 09:00
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 10.1097/HJH.0b013e32832dda6f [doi]
PST - ppublish
SO  - J Hypertens. 2009 Sep;27(9):1855-62. doi: 10.1097/HJH.0b013e32832dda6f.