PVN Blockade of p44/42 MAPK Pathway Attenuates Salt-induced Hypertension through Modulating Neurotransmitters and Attenuating Oxidative Stress

作者：Hong‐Li Gao, Xiao‐Jing Yu, Kai‐Li Liu, Xiao‐Lian Shi, Jie Qi, Yanmei Chen, Yan Zhang, Juan Bai, Qiu-Yue Yi, Zhipeng Feng, Wensheng Chen, Wei Cui, Jinjun Liu, Guo‐Qing Zhu, Yu‐Ming Kang · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/srep43038 · 被引用次数：29 · 研究领域：Regulation of Appetite and Obesity、Neuroscience of respiration and sleep、Neuroendocrine regulation and behavior

The imbalance of neurotransmitters and excessive oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether blockade of p44/42 MAPK pathway in the hypothalamic paraventricular nucleus (PVN) ameliorates the development of hypertension through modulating neurotransmitters and attenuating oxidative stress. Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 6 weeks and were treated with bilateral PVN infusion of PD-98059 (0.025 μg/h), a p44/42 MAPK inhibitor, or vehicle via osmotic minipump. HS resulted in higher mean arterial pressure (MAP) and Fra-like (Fra-LI) activity, and plasma and PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. PD-98059 infusion reduced NE, TH, NOX2 and NOX4 in the PVN, and induced Cu/Zn-SOD and GAD67 in the PVN. It suggests that PVN blockade of p44/42 MAPK attenuates hypertension through modulating neurotransmitters and attenuating oxidative stress.