Angiotensin II can induce
oxidant stress by stimulating vascular
superoxide production.
Hypertension promotes mitochondrial function decline in brain, liver and heart. The aim of this study was to investigate whether a)
hypertension is associated to kidney
mitochondrial dysfunction, and b)
angiotensin II blockade can reverse potential mitochondrial changes in
hypertension. Four-month-old male spontaneously hypertensive rats (SHR) received
drinking water containing
candesartan (7.5 mg/kg/day, SHR+Cand), or no additions (SHR) for 4-months. Eight-month-old Wistar-Kyoto rats (WKY), that received water with no additions, were used as control. Systolic blood pressure,
proteinuria, cortical glomerular area, and glomerular and tubulointerstitial alpha-smooth muscle actin labeling, were significantly higher, and
creatinine clearance was significantly lower, in SHR relative to WKY and SHR+Cand. In SHR, kidney mitochondria membrane potential, and
nitric oxide synthase and
cytochrome oxidase activities were significantly lower than in WKY and SHR+Cand. In SHR, mitochondrial
hydrogen peroxide production was significantly higher than in WKY and SHR+Cand. The results suggest that, in
hypertension, increased mitochondrial
oxidant production may mediate kidney
mitochondria dysfunction.
Candesartan preserved mitochondrial function, probably favoring the maintenance of adequate cellular and tissue function in the kidney. The known renal protective effects of
candesartan in
hypertension may be related to the improvement of mitochondrial function. This may be an additional or alternative explanation for some of the beneficial effects of AT1 receptor antagonists.