Rac1/NAD(P)H Oxidase‐derived Reactive Oxygen Species in the Nucleus Tractus Solitarius are Involved in the Neural Mechanisms of Hypertension of SHRSP

Reactive oxygen species (ROS) in the central nervous system (CNS) are thought to contribute to sympathoexcitation in cardiovascular diseases such as hypertension and heart failure. The nucleus tractus solitarius (NTS) has an important role in cardiovascular regulation, however, the role of ROS in the NTS remains unclear. We examined whether increased oxidative stress in the NTS of stroke‐prone spontaneously hypertensive rats (SHRSP) is the result of enhanced ROS production or suppressed ROS clearance. NAD(P)H oxidase, which is a major source of ROS in the CNS, was activated in the NTS of SHRSP. Cu/Zn superoxide dismutase (Cu/Zn‐SOD) protein expression and activity were decreased in the NTS of SHRSP. More importantly, selective inhibition of Rac1, a small G‐protein involved in the activation of NAD(P)H oxidase, in the NTS decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSP, but not in Wistar‐Kyoto (WKY) rats. In addition, overexpression of Cu/Zn‐SOD in the NTS of SHRSP, but not WKY rats, also decreased blood pressure, heart rate, and urinary norepinephrine excretion. These observations indicate that both enhanced ROS production and suppressed scavenging of cytosolic ROS contribute to increased oxidative stress in the NTS of SHRSP. Furthermore, increased oxidative stress in the NTS of SHRSP might contribute to the neural mechanisms of hypertension.