Integrative Physiology Transcriptional Upregulation of Brain-Derived Neurotrophic Factor in Rostral Ventrolateral Medulla by Angiotensin II Significance in Superoxide Homeostasis and Neural Regulation of Arterial Pressure

Rationale: Oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of neurogenic vasomotor tone are located, contributes to neural mechanisms of hypertension. Emerging evidence suggests that brain-derived neurotrophic factor (BDNF) manifests " nontrophic " actions. Objective: We assessed the hypothesis that BDNF plays an active role in oxidative stress–associated neurogenic hypertension by maintaining superoxide anion (O 2 .) homeostasis in RVLM. Key Words: brain-derived neurotrophic factor Ⅲ oxidative stress Ⅲ angiotensin II Ⅲ mitochondrial uncoupling protein Ⅲ blood pressure O xidative stress resulting from an imbalance of production over degradation of the reactive oxygen species (ROS), particularly superoxide anion (O 2 .), is associated with hypertension. 1,2 In the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of vasomotor tone are located, 3 overproduction of O 2. plays a pivotal role in neural mechanism of hypertension by increasing sympathetic outflow to the peripheral blood vessels. 1,2,4 – 6 Thus, NADPH oxidase– derived O 2. in RVLM mediates chronic pressor response induced by angiotensin II (Ang II). 7 A decrease in molecular synthesis and enzyme activity of superoxide dismutase (SOD) isoforms contributes to hyper-tensive phenotype in the spontaneously hypertensive rats (SHRs). 6 On the other hand, transcriptional upregulation of mitochondrial uncoupling protein (UCP)2 abrogates Ang II–induced oxidative stress and alleviates oxidative stress– associated neurogenic hypertension via a negative-feedback mechanism. 8 One of the well-recognized protective mechanisms against stressful insults in brain is expression of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF). 9 Superimposed on its " classic " trophic functions in proliferation , differentiation, and survival of neurons in the peripheral and central nervous system during development, 10 or in