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

Autor: Gao HL; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Yu XJ; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Liu KL; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Shi XL; Department of Pharmacology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China., Qi J; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Chen YM; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Zhang Y; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Bai J; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Yi QY; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Feng ZP; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Chen WS; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China., Cui W; Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China., Liu JJ; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China., Zhu GQ; Department of Physiology, Nanjing Medical University, Nanjing 210029, China., Kang YM; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Feb 22; Vol. 7, pp. 43038. Date of Electronic Publication: 2017 Feb 22.
DOI: 10.1038/srep43038
Abstrakt: 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: MEDLINE