Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats
| Autor: | Em, Cavanagh, Je, Toblli, Ferder L, Piotrkowski B, Stella I, Cg, Fraga, Felipe Inserra |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Kidney Cortex Angiotensin II Biphenyl Compounds Tetrazoles Blood Pressure Hydrogen Peroxide Immunohistochemistry Rats Inbred WKY Actins Membrane Potentials Mitochondria Rats Electron Transport Complex IV Oxidative Stress Creatinine Rats Inbred SHR Hypertension Animals Benzimidazoles Nitric Oxide Synthase Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1165-158X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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