Abstract 933: Increased Reactive Oxygen Species in the Nucleus Tractus Solitarius are Involved in the Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
Background: 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. NAD(P)H oxidase is a major source of ROS in the CNS, and mediates angiotensin II signaling in neurons. The nucleus tractus solitarius (NTS), which receives afferent input from baroreceptors, have an important role in cardiovascular regulation. The role of ROS in the NTS, however, is not understood. The aim of the present study was to examine 1) whether ROS generation is increased in the NTS of stroke-prone spontaneously hypertensive rats (SHRSP), 2) whether ROS scavenging is decreased in the NTS of SHRSP, 3)and whether ROS in the NTS is involved in the neural mechanisms of hypertension.
Methods: ROS generation in the NTS of SHRSP and WKY was evaluated by measuring thiobarbituric acid-reactive substances (TBARS) levels. NADPH oxidase activity was measured by lucigenin luminescence and Cu/Zn supeoxide dismutase (Cu/SnSOD) activity was assayed by reduction of cytochrome c. The role of ROS in the NTS of SHRSP in cardiovascular regulation was evaluated using two different methods; transfection of either adenovirus encoding human Cu/Zn superoxide dismutase (AdCu/ZnSOD) to scavenge cytosolic superoxide or adenovirus encoding dominant-negative Rac1 (AdDN17Rac1) to suppress ROS generation by NAD(P)H oxidase in the NTS. Mean blood pressure (MBP) and heart rate (HR) were measured using a radio-telemetry system. Urinary norepinephrine excretion for 24 hours was measured as an indicator of sympathetic nerve activity.
Results: TBARS levels and NAD(P)H oxidase activity in the NTS were greater in SHRSP than in WKY. Cu/ZnSOD protein expression and SOD activity in the NTS was lower in SHRSP than in WKY. Transfection of either AdCu/ZnSOD or AdN17Rac1 into the NTS decreased MBP, HR, and urinary norepinephrine excretion in SHRSP.
Conclusions: These results suggest that the increased ROS in the NTS of SHRSP contribute to the neural mechanisms of hypertension. Furthermore, both the accelerated ROS production and suppressed scavenging of cytosolic ROS might contribute to increased oxidative stress in the NTS of SHRSP.