Angiotensin type-1 receptor blocker candesartan inhibits calcium oxalate crystal deposition in ethylene glycol-treated rat kidneys.
OBJECTIVE
To investigate whether an angiotensin type-1 receptor blocker could inhibit calcium oxalate crystal deposition using ethylene glycol-treated rats. The renoprotective effect has been reported to be another role of angiotensin type-1 receptor blockers in addition to their role in lowering blood pressure. Recent research has suggested that inhibiting reactive oxidative species generation and tubulointerstitial inflammation is the major role of angiotensin type-1 receptor blockers. These 2 factors are also important in the mechanism of calcium oxalate stone formation.


METHODS
We divided 28 rats, aged 7 weeks, into 4 groups: group 1, control rats; group 2, candesartan-treated rats; group 3, stone-forming rats; and group 4, candesartan-treated stone-forming rats. The kidney crystal deposits were examined, and the oxidative stress biomarker, nicotinamide adenine dinucleotide phosphate oxidase activity, general and urinary variables, and the transforming growth factor-β level in kidney tissue were compared among the 4 groups.


RESULTS
The candesartan-treated rats were healthy and had weight gain similar to that of the control rats, although a significant reduction in blood pressure was observed. The urinary components associated with calcium oxalate stone formation were not influenced by candesartan treatment; however, significantly fewer crystal deposits were observed in group 4. The oxidative biomarker and nicotinamide adenine dinucleotide phosphate oxidase activity decreased, and the level of transforming growth factor-β was suppressed in group 4.


CONCLUSIONS
Candesartan had substantial effects on crystal formation in the rat kidney by suppressing nicotinamide adenine dinucleotide phosphate oxidase and the transforming growth factor-β levels.
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Iwao
I
Yoshioka
Masao
M
Tsujihata
Wongswat
W
Akanae
Norio
N
Nonomura
Akihiko
A
Okuyama
D000080242:8-Hydroxy-2'-Deoxyguanosine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002129:Calcium Oxalate / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D007669:Kidney Calculi / Q000737:chemistry / Q000517:prevention & control*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D002129:Calcium Oxalate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; D003849:Deoxyguanosine; C081643:candesartan