Role of Racl-derived reactive oxygen species in the vasomotor center of the brain in hypertension

大脑中的活性氧增加交感神经系统的活动。这种机制有助于高血压的神经机制。孤束核（NTS）和延髓头端腹外侧区（RVLM）是脑干内决定基础交感神经系统活动和压力反射功能的关键部位。因此，这些区域被称为血管中心。NAD（P）H氧化酶是活性氧的主要来源，其活化由小G蛋白Racl介导。然而，Racl/NAD（P）H氧化酶衍生的活性氧在高血压脑干中的作用尚不清楚。因此，本研究的目的是确定在易卒中的自发性高血压大鼠（SHRSP）的脑干中Racl的抑制是否减少活性氧的产生，从而降低该模型中的血压。我们将显性阴性Racl转染到NTS中，并使用无线电遥测仪观察血压。 关于我们 y在清醒的SHRSP和血压正常的Wistar-Kyoto大鼠（WKY）中。Racl在NTS中的活性SHRSP高于WKY。显性阴性Racl转染NTS降低血压，心率，和尿去甲肾上腺素排泄SHRSHP，但不WKY。Racl的抑制还减弱NTS中NAD（P）H氧化酶活性和活性氧物质产生。NTS中Cu/Zn-SOD的过表达也降低了SHRSP的血压、心率和尿去甲肾上腺素排泄，表明清除活性氧抑制交感神经系统活性，从而降低血压。这些结果表明，脑干中Racl源性活性氧参与了SHRSP高血压的神经机制，同时也证实了脑干中另一种小G蛋白Rho在循环的神经控制中起重要作用。此外，一些抗高血压药物可能会减少大脑中的活性氧。少

Reactive oxygen species in the brain increase sympathetic nervous system activity. This mechanism contributes to neural mechanism(s) of hypertension. The nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM) are key sites in the brain stem for determining the basal sympathetic nervous system activity and baroreflex functon. Therefore, these areas are so called the vasomotor center. NAD(P)H oxidase is a major source of reactive oxygen species and its activation is mediated by small G protein Racl. However, the role of Racl/NAD(P)H oxidase-derived reactive oxygen species in the brain stem of hypertension is not known. Therefore, the aim of the present study was to determine whether inhibition of Racl in the brain stem of stroke-prone spontaneously hypertensive rats (SHRSP) decreases reactive oxygen species generation, thereby reducing blood pressure in this model. We transfected dominant-negative Racl into the NTS and observed blood pressure using a radio-telemetr … More y in conscious SHRSP and normotensive Wistar-Kyoto rats (WKY). Racl activity in the NTS was greater in SHRSP than in WKY. Transfection of dominant-negative Racl into the NTS decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSHP, but not in WKY. Inhibition of Racl also attenuated NAD(P)H oxidase activity in the NTS and reactive oxygen species generation. Overexpression of Cu/Zn-SOD in the NTS also reduced blood pressure, heart rate, and urinary norepinephrine excretion in SHRSP, suggesting that scavenging reactive oxygen species inhibits sympathetic nervous system activity thereby reducing blood pressure. These results indicate that Racl-derived reactive oxygen species in the brain stem contribute to neural mechanism(s) of hypertension of SHRSP.We also demonstrated another small G protein Rho in the brain stem plays an important role in neural control of circulation. In addition, some antihypertensive drugs might reduce reactive oxygen species in the brain. Less