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

大脑中的活性氧会增加交感神经系统的活动。这一机制有助于高血压的神经机制(S)。孤束核(NTS)和延髓头端腹外侧核(RVLM)是决定交感神经系统基础活动和压力感受性反射功能的关键部位。因此，这些区域被称为血管运动中心。NAD(P)H氧化酶是活性氧的主要来源，其激活是由小G蛋白Rac1介导的。然而，Racl/NAD(P)H氧化酶衍生的活性氧物种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抑制卒中易感型自发性高血压大鼠(SHRSP)脑干中RACL是否减少了活性氧的产生，从而降低了该模型的血压。我们将显性阴性的racl基因导入nts，并用无线遥测…观察血压。清醒的SHRSP大鼠和血压正常的Wistar-京都大鼠(WKY)的血压更高。SHRSP组NTS的RACL活性高于WKY组。将显性负性racl基因导入NTS可降低SHRSHP大鼠的血压、心率和尿去甲肾上腺素排泄量，但对WKY大鼠无明显影响。抑制Racl还可抑制NTS中NAD(P)H氧化酶的活性和活性氧的产生。在NTS中铜/锌-超氧化物歧化酶的过表达也降低了SHRSP的血压、心率和尿去甲肾上腺素的排泄，这表明清除活性氧会抑制交感神经系统的活动，从而降低血压。这些结果表明，脑干Racl衍生的活性氧物种参与了SHRSP高血压的神经机制(S)。我们还证明了脑干中的另一种小G蛋白Rho在神经循环调控中起重要作用。此外，一些降压药可能会减少大脑中的活性氧。较少

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