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29.04.2019 | Ausgabe 5/2019

Cardiovascular Toxicology 5/2019

Carbon Monoxide Attenuates High Salt-Induced Hypertension While Reducing Pro-inflammatory Cytokines and Oxidative Stress in the Paraventricular Nucleus

Zeitschrift:
Cardiovascular Toxicology > Ausgabe 5/2019
Autoren:
Dong-Dong Zhang, Yan-Feng Liang, Jie Qi, Kai B. Kang, Xiao-Jing Yu, Hong-Li Gao, Kai-Li Liu, Yan-Mei Chen, Xiao-Lian Shi, Guo-Rui Xin, Li-Yan Fu, Yu-Ming Kang, Wei Cui
Wichtige Hinweise
Handling Editor: Rajiv Janardhanan.

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12012-019-09517-w) contains supplementary material, which is available to authorized users.
Dong-Dong Zhang and Yan-Feng Liang have contributed equally to this work.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Carbon monoxide (CO) presents anti-inflammatory and antioxidant activities as a new gaseous neuromessenger produced by heme oxygenase-1 (HO-1) in the body. High salt-induced hypertension is relevant to the levels of pro-inflammatory cytokines (PICs) and oxidative stress in the hypothalamic paraventricular nucleus (PVN). We explored whether CO in PVN can attenuate high salt-induced hypertension by regulating PICs or oxidative stress. Male Dahl Salt-Sensitive rats were fed high-salt (8% NaCl) or normal-salt (0.3% NaCl) diet for 4 weeks. CORM-2, ZnPP IX, or vehicle was microinjected into bilateral PVN for 6 weeks. High-salt diet increased the levels of MAP, plasma norepinephrine (NE), reactive oxygen species (ROS), and the expressions of COX2, IL-1β, IL-6, NOX2, and NOX4 significantly in PVN (p < 0.05), but decreased the expressions of HO-1 and Cu/Zn-SOD in PVN (p < 0.05). Salt increased sympathetic activity as measured by circulating norepinephrine, and increased the ratio of basal RSNA to max RSNA, in part by decreasing max RSNA. PVN microinjection of CORM-2 decreased the levels of MAP, NE, RSNA, ROS and the expressions of COX2, IL-1β, IL-6, NOX2, NOX4 significantly in PVN of hypertensive rat (p < 0.05), but increased the expressions of HO-1 and Cu/Zn-SOD significantly (p < 0.05), which were all opposite to the effects of ZnPP IX microinjected in PVN (p < 0.05). We concluded that exogenous or endogenous CO attenuates high salt-induced hypertension by regulating PICs and oxidative stress in PVN.

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Zusatzmaterial
Supplementary material 1 (PPTX 79 kb)
12012_2019_9517_MOESM1_ESM.pptx
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