Published online before print July 6, 2009, doi: 10.1161/HYPERTENSIONAHA.109.130351
(Hypertension. 2009;54:322.)
© 2009 American Heart Association, Inc.
Original Articles |
Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy
From the British Heart Foundation Glasgow Cardiovascular Research Centre (D.G., N.N.H., C.A.H., E.B., A.F.D.), Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom; Department of Chemistry (R.A.J.S.), University of Otago, Dunedin, New Zealand; Medical Research Council Mitochondrial Biology Unit (H.M.C., M.P.M.), Cambridge, United Kingdom.
Correspondence to Anna F. Dominiczak, BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, 126 University Pl, Glasgow, G12 8TA United Kingdom. E-mail a.dominiczak{at}clinmed.gla.ac.uk
Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ10. Eight-week–old male stroke-prone spontaneously hypertensive rats were treated with MitoQ10 (500 µmol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 µmol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by 
25 mm Hg over the 8-week MitoQ10 treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ10 treatment significantly improved thoracic aorta NO bioavailability (1.16±0.03 g/g; P=0.002, area under the curve) compared with both untreated controls (0.68±0.02 g/g) and decylTPP-treated rats (0.60±0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ10 treatment compared with untreated control and decylTPP treatment (MitoQ10: 4.01±0.05 mg/g; control: 4.42±0.11 mg/g; and decylTPP: 4.40±0.09 mg/g; ANOVA P=0.002). Total MitoQ10 content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ10-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ10, with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ10 protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ10 provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease.
Key Words: hypertension • hypertrophy • mitochondria • antioxidant • endothelial function
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