Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy

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, MitoQ(10). Eight-week-old male stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500 mu mol/L; n = 16), control compound decyltriphenylphosphonium (decylTPP; 500 mu mol/L; n = 8), or vehicle (n = 9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by approximate to 25 mm Hg over the 8-week MitoQ(10) treatment period compared with decylTPP (F = 5.94; P = 0.029) or untreated controls (F = 65.6; P = 0.0001). MitoQ(10) 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 MitoQ(10) treatment compared with untreated control and decylTPP treatment (MitoQ(10): 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 MitoQ(10) content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ(10), with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10) protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ(10) provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease. (Hypertension. 2009; 54: 322-328.)