PVN Blockade of p44/42 MAPK Pathway Attenuates Salt-induced Hypertension through Modulating Neurotransmitters and Attenuating Oxidative Stress
Autor: | Wei Cui, Yan Zhang, Xiao-Lian Shi, Qiu-Yue Yi, Wen-Sheng Chen, Zhi-Peng Feng, Kai-Li Liu, Yan-Mei Chen, Jin-Jun Liu, Xiao-Jing Yu, Yu-Ming Kang, Hong-Li Gao, Juan Bai, Guo-Qing Zhu, Jie Qi |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway endocrine system medicine.medical_specialty Glutamate decarboxylase Sodium Chloride 030204 cardiovascular system & hematology medicine.disease_cause Article Superoxide dismutase 03 medical and health sciences Norepinephrine 0302 clinical medicine Internal medicine medicine Animals Mitogen-Activated Protein Kinase 1 Neurotransmitter Agents Mitogen-Activated Protein Kinase 3 Rats Inbred Dahl Multidisciplinary Tyrosine hydroxylase biology Chemistry NOX4 Blockade Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology nervous system Hypertension biology.protein hormones hormone substitutes and hormone antagonists Oxidative stress Paraventricular Hypothalamic Nucleus Signal Transduction medicine.drug |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep43038 |
Popis: | 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. |
Databáze: | OpenAIRE |
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