Abstract 16022: Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension by Modulating Paraventricular Nucleus of Hypothalamus
Background: Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of the brainstem play a pivotal role in the neural mechanism of hypertension. The paraventricular nucleus of the hypothalamus (PVN) is an important nucleus to control sympathetic outflow and thereby arterial pressure via projections to the RVLM. Both regions are well studied, but how they interact with each other and contribute to sympathoexcitation in hypertension remains poorly understood.
Hypothesis: The aim of this study was to examine whether increased ROS in the RVLM modulate sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertension.
Methods and Results: We used male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We transfected adenovirus vectors encoding manganese superoxide dismutase gene (SOD, known to decrease ROS levels) or β-galactosidase gene (LacZ) bilaterally into the RVLM. Mean arterial pressure (MAP, telemetry) was significantly lowered after the transfection in only SOD-SHR (Day7 vs. Day0, 143±4 vs. 168±4mmHg, p<0.05, n=5). Oxidative stress levels in the RVLM evaluated by TBARS were significantly reduced in SOD-SHR compared with LacZ-SHR (0.38±0.04 vs. 0.73±0.03μmol/g wet weight, p<0.05, n=5). We microinjected bicuculline (GABA-A receptor antagonist, 100 pmol) and muscimol (GABA-A receptor agonist, 100 pmol) into the PVN on day 7. Bicuculline microinjection into the PVN increased MAP and renal sympathetic nerve activity (RSNA) in all groups. The pressor responses and the change in RSNA were significantly attenuated in SOD-SHR compared with LacZ-SHR (ΔMAP/baseline MAP [%], 7.4±0.5 vs. 11.3±1.2%, p<0.05, n=5; the change in RSNA (%baseline), 32.6±1.2 vs. 49.6±3.1%, p<0.05, n=5), but not in SOD-WKY compared with LacZ-WKY. Microinjection of muscimol into the PVN decreased MAP in all groups. When the depressor responses were greatest, however, MAP was significantly lower in SOD-SHR compared with LacZ-SHR (96±5 vs. 139±4mmHg, p<0.05, n=5), but not in SOD-WKY compared with LacZ-WKY.
Conclusions: ROS in the RVLM contribute to maintain high blood pressure via sympathoexcitation in this region as well as augmentation of the pressor and sympathoexcitatory response induced by the PVN in SHR.
- © 2010 by American Heart Association, Inc.