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  • Title: Carbon Monoxide Attenuates High Salt-Induced Hypertension While Reducing Pro-inflammatory Cytokines and Oxidative Stress in the Paraventricular Nucleus.
    Author: Zhang DD, Liang YF, Qi J, Kang KB, Yu XJ, Gao HL, Liu KL, Chen YM, Shi XL, Xin GR, Fu LY, Kang YM, Cui W.
    Journal: Cardiovasc Toxicol; 2019 Oct; 19(5):451-464. PubMed ID: 31037602.
    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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