Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of
hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important
transcription factor that modulates cell
antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of
tert-butylhydroquinone (
tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of
tBHQ (0.8μg/day), or
oxygen free radical scavenger tempol (20μg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma
norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1),
superoxide dismutase-1 (SOD1) and
catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of
tBHQ or
tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition,
tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore,
tBHQ attenuated PVN levels of ROS, the expression of proinflammatory
cytokines and restored the imbalance of
neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated
small interfering RNA abrogated the protective effects of
tBHQ on
hypertension. These findings suggest that PVN administration of
tBHQ can attenuate
hypertension by activation of the Nrf2-mediated signaling pathway.