Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates neurohormonal excitation in high salt-induced hypertension.

Abstract

Reactive oxygen species (ROS) in the brain plays an important role in the progression of hypertension and hydrogen peroxide (H2O2) is a major component of ROS. The aim of this study is to explore whether endogenous H2O2 changed by polyethylene glycol-catalase (PEG-CAT) and aminotriazole (ATZ) in the hypothalamic paraventricular nucleus (PVN) regulates neurotransmitters, renin-angiotensin system (RAS), and cytokines, and whether subsequently affects the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in high salt-induced hypertension. Male Sprague-Dawley rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 10 weeks. Then rats were treated with bilateral PVN microinjection of PEG-CAT (0.2 i.u./50nl), an analog of endogenous catalase, the catalase inhibitor ATZ (10nmol/50nl) or vehicle. High salt-fed rats had significantly increased MAP, RSNA, plasma norepinephrine (NE) and pro-inflammatory cytokines (PICs). In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), interleukin-1beta (IL-1β), glutamate and NE, and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN than normal diet rats. Bilateral PVN microinjection of PEG-CAT attenuated the levels of RAS and restored the balance of neurotransmitters and cytokines, while microinjection of ATZ into the PVN augmented those changes occurring in hypertensive rats. Our findings demonstrate that ROS component H2O2 in the PVN regulating MAP and RSNA are partly due to modulate neurotransmitters, renin-angiotensin system, and cytokines within the PVN in salt-induced hypertension.

• Authors: Meng Zhang, Da-Nian Qin, Yu-Ping Suo, Qing Su, Hong-Bao Li, Yu-Wang Miao, Jing Guo, Zhi-Peng Feng, Jie Qi, Hong-Li Gao, Jian-Jun Mu, Guo-Qing Zhu, Yu-Ming Kang
• Journal: Toxicology letters (Toxicol Lett) Vol. 235 Issue 3 Pg. 206-15 (Jun 15 2015) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 25891026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Neurotransmitter Agents
• Sodium Chloride, Dietary
• catalase-polyethylene glycol
• Polyethylene Glycols
• Hydrogen Peroxide
• Catalase
• Amitrole

Topics

• Amitrole (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Catalase (pharmacology)
• Gene Expression Regulation (drug effects)
• Heart Rate (drug effects)
• Hydrogen Peroxide (metabolism)
• Hypertension (chemically induced)
• Male
• Neurotransmitter Agents (blood, metabolism)
• Paraventricular Hypothalamic Nucleus (metabolism)
• Polyethylene Glycols (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sodium Chloride, Dietary (toxicity)