Pharmacobiochemical Laboratory of Third Department of Internal Medicine, Faculty of Medicine, Comenius University, Spitálska 24, 81372 Bratislava, Slovak Republic.
Cell Mol Neurobiol. 2010 Jul;30(5):751-8. doi: 10.1007/s10571-010-9501-4. Epub 2010 Feb 10.
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.
自由基的产生增加和线粒体功能的损害是高血压发病机制中的重要因素。本研究探讨了高血压对脑线粒体呼吸链功能、辅酶 Q(9) (CoQ(9))、辅酶 Q(10) (CoQ(10))和α-生育酚含量的影响，以及血管紧张素 II 型 1 型受体（AT1R）阻断在高血压前期对这些参数的影响。此外，还评估了血压、心脏和脑重与体重的比值，以及供应大脑的基底动脉的几何形状。第 9 周时，与 Wistar 大鼠（WR）相比，自发性高血压大鼠（SHR）的血压和心脏重量/体重比显著升高，脑重量/体重比显著降低。SHR 的基底动脉横截面积增加。谷氨酸支持的呼吸、ATP 产生率以及 CoQ(9)、CoQ(10)和α-生育酚的浓度降低。琥珀酸支持的功能和细胞色素氧化酶活性没有改变。从 4 周到 9 周龄开始，用氯沙坦（20 mg/kg/天）治疗 SHR 可预防高血压、心脏和动脉壁肥大以及脑重/体重下降。治疗后，与未经治疗的 SHR 相比，ATP 产生率和 CoQ 浓度增加。脑线粒体中能量产生受损和脂溶性抗氧化剂水平降低以及基底动脉结构改变可能导致高血压时脑组织易损性增加。长期使用 AT1R 阻滞剂可能预防高血压中的脑功能障碍。
