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Carbon Monoxide Attenuates High Salt-Induced Hypertension While Reducing Pro-inflammatory Cytokines and Oxidative Stress in the Paraventricular Nucleus.
- Source :
-
Cardiovascular toxicology [Cardiovasc Toxicol] 2019 Oct; Vol. 19 (5), pp. 451-464. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Anti-Inflammatory Agents metabolism
Antihypertensive Agents metabolism
Antioxidants metabolism
Carbon Monoxide metabolism
Cyclooxygenase 2 metabolism
Disease Models, Animal
Heme Oxygenase (Decyclizing) metabolism
Hypertension metabolism
Hypertension physiopathology
Male
Organometallic Compounds metabolism
Paraventricular Hypothalamic Nucleus metabolism
Paraventricular Hypothalamic Nucleus physiopathology
Rats, Inbred Dahl
Sodium Chloride, Dietary
Anti-Inflammatory Agents pharmacology
Antihypertensive Agents pharmacology
Antioxidants pharmacology
Arterial Pressure drug effects
Carbon Monoxide pharmacology
Cytokines metabolism
Hypertension prevention & control
Inflammation Mediators metabolism
Organometallic Compounds pharmacology
Oxidative Stress drug effects
Paraventricular Hypothalamic Nucleus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0259
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cardiovascular toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 31037602
- Full Text :
- https://doi.org/10.1007/s12012-019-09517-w