Mitochondrial Respiratory Chain Dysfunction in the Brain is not a Major Component of Increased Reactive Oxygen Species in Neural Mechanisms of Hypertension

Abstract

We reported reactive oxygen species (ROS) are increased in the brain of stroke-prone spontaneously hypertensive rats (SHRSP), and play an important role in neural mechanisms of hypertension. Mitochondria is a major source of ROS, and mitochondrial dysfunction and mitochondrial DNA damage are reported in neurological diseases and aging. However, the role of mitochondria as a source of ROS, particularly in the brain remains unknown. The aim of the present study was thus to determine whether mitochondrial dysfunction and mitochondria-derived ROS in the brain of SHRSP are involved in the mechanism of ROS production. Thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, brainstem) were significantly higher in SHRSP (22 weeks-old) than in WKY. However, TBARS levels of mitochondrial fraction in each area of the brain were comparable between the two groups. Furthermore, we found no alteration in mitochondrial respiratory complex activities, mitochondrial DNA copy numbers, and mitochondrial mRNA levels in the brain of SHRSP. Intracisternal infusion of diphenylene iodonium (DPI), an inhibitor of NAD(P)H oxidase, decreased blood pressure. These results suggest that mitochondria in the brain of SHRSP is not damaged, and, together with the results of our previous study, ROS derived by mitochondrial respiratory chain dysfunction is not involved in neural mechanisms of hypertension. The NAD(P)H oxidase may be important as a source of ROS in the brain of SHRSP.