Losartan improved respiratory function and coenzyme Q content in brain mitochondria of young spontaneously hypertensive rats.
Increased production of free radicals and impairment of mitochondrial function are important factors in the pathogenesis of hypertension. This study examined the impact of hypertension on mitochondrial respiratory chain function, coenzyme Q(9) (CoQ(9)), coenzyme Q(10) (CoQ(10)), and alpha-tocopherol content in brain mitochondria, and the effect of blockade of angiotensin II type 1 receptors (AT1R) in the prehypertensive period on these parameters. In addition, blood pressure, heart and brain weight to body weight ratios, and the geometry of the basilar artery supplying the brain were evaluated. In the 9th week blood pressure and heart weight/body weight ratio were significantly increased and brain weight/body weight ratio was significantly decreased in spontaneously hypertensive rats (SHR) when compared to Wistar rats (WR). The cross-sectional area of the basilar artery was increased in SHR. Glutamate-supported respiration, the rate of ATP production, and concentrations of CoQ(9), CoQ(10), and alpha-tocopherol were decreased in SHR. The succinate-supported function and cytochrome oxidase activity were not changed. The treatment of SHR with losartan (20 mg/kg/day) from 4th to 9th week of age exerted preventive effect against hypertension, heart and arterial wall hypertrophy, and brain weight/body weight decline. After the therapy, the rate of ATP production and the concentration of CoQ increased in comparison to untreated SHR. The impairment of energy production and decreased level of lipid-soluble antioxidants in brain mitochondria as well as structural alterations in the basilar artery may contribute to increased vulnerability of brain tissue in hypertension. Long-term treatment with AT1R blockers may prevent brain dysfunction in hypertension.
Pharmacobiochemical Laboratory of Third Department of Internal Medicine, Faculty of Medicine, Comenius University, Spitálska 24, 81372 Bratislava, Slovak Republic. zuzana.sumbalova@zoznam.sk
Z
Z
Sumbalová
J
J
Kucharská
F
F
Kristek
D000375:Aging / Q000187:drug effects*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology; D019802:Succinic Acid / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D005971:Glutamates; D012402:Rotenone; D014451:Ubiquinone; D019802:Succinic Acid; D003576:Electron Transport Complex IV; C024989:coenzyme Q10; D024502:alpha-Tocopherol; D019808:Losartan