Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats.

Abstract

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.

• Authors: E M V De Cavanagh, J E Toblli, L Ferder, B Piotrkowski, I Stella, C G Fraga, F Inserra
• Journal: Cellular and molecular biology (Noisy-le-Grand, France) (Cell Mol Biol (Noisy-le-grand)) Vol. 51 Issue 6 Pg. 573-8 (Nov 08 2005) ISSN: 1165-158X [Electronic] France
• PMID: 16309582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• Tetrazoles
• smooth muscle actin, rat
• Angiotensin II
• Creatinine
• Hydrogen Peroxide
• Nitric Oxide Synthase
• Electron Transport Complex IV
• candesartan

Topics

• Actins (analysis)
• Angiotensin II (physiology)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Blood Pressure (drug effects)
• Creatinine (urine)
• Electron Transport Complex IV (analysis)
• Hydrogen Peroxide (analysis)
• Hypertension (physiopathology)
• Immunohistochemistry
• Kidney Cortex (drug effects, pathology, physiopathology)
• Male
• Membrane Potentials (drug effects)
• Mitochondria (chemistry, drug effects, physiology)
• Nitric Oxide Synthase (analysis)
• Oxidative Stress (physiology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Tetrazoles (pharmacology)