Hypothalamic and inflammatory basis of hypertension

Khor, Sinan; Cai, Dongsheng

doi:10.1042/cs20160001

Cited by 33 publications

(40 citation statements)

References 176 publications

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“…Additionally, cytokines have different functions in the central nervous system and can induce neurotoxicity, which appears to contribute to the physiopathology of psychiatric [depression, schizophrenia] and neurodegenerative diseases [Parkinson’s and Alzheimer’s diseases] (Allan and Rothwell, 2003; Corsi-Zuelli et al, 2017; Dantzer et al, 2008). Moreover, since inflammation in the central nervous system, particularly in the hypothalamus, has recently been shown to be intricately involved in the development and maintenance of hypertension (Khor and Cai, 2017), we suggest that the selective and central anti-inflammatory potential of ADN stimulation could be an additional mechanism involved in the baroreflex anti-hypertensive effects.…”

Section: Discussionmentioning

confidence: 90%

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

et al. 2018

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We previously reported that activation of the baroreflex, a critical physiological mechanism controlling cardiovascular homeostasis, through electrical stimulation of the aortic depressor nerve attenuates joint inflammation in experimental arthritis. However, it is unknown whether baroreflex activation can control systemic inflammation. Here, we investigate whether baroreflex activation controls systemic inflammation in conscious endotoxemic rats. Animals underwent sham or electrical aortic depressor nerve stimulation initiated 10 min prior to a lipopolysaccharide (LPS) challenge, while inflammatory cytokine levels were measured in the blood, spleen, heart and hypothalamus 90 min after LPS treatment. Baroreflex activation did not affect LPS-induced levels of pro-inflammatory (tumor necrosis factor, interleukin 1β and interleukin 6) or anti-inflammatory (interleukin 10) cytokines in the periphery (heart, spleen and blood). However, baroreflex stimulation attenuated LPS-induced levels of all these cytokines in the hypothalamus. Notably, these results indicate that the central anti-inflammatory mechanism induced by baroreflex stimulation is independent of cardiovascular alterations, since aortic depressor nerve stimulation that failed to induce hemodynamic changes was also efficient at inhibiting inflammatory cytokines in the hypothalamus. Thus, aortic depressor nerve stimulation might represent a novel therapeutic strategy for neuroprotection, modulating inflammation in the central nervous system.

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Section: Discussionmentioning

confidence: 90%

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

et al. 2018

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“…Studies have also confirmed that acupuncture can inhibit reflex hypertension through the opioid-mediated inhibition of glutamate in rVLM 32 . Therefore, glutamatergic suppression may further reverse the hypertensive effect of central TNF-α, which simultaneously recovers blood pressure and energy balance via inhibiting NF-κB and IKK β activation 33,34 (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

Active Acupoints Differ from Inactive Acupoints in Modulating Key Plasmatic Metabolites of Hypertension: A Targeted Metabolomics Study

Yang

Zheng

Chen

et al. 2018

Sci Rep

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The effect of active acupoints versus inactive acupoints in treating hypertension is not well documented. Metabolic phenotypes, depicted by metabolomics analysis, reflect the influence of external exposures, nutrition, and lifestyle on the integrated system of the human body. Therefore, we utilized high-performance liquid chromatography tandem mass spectrometry to compare the targeted metabolic phenotype changes induced by two different acupoint treatments. The clinical outcomes show that active acupoint treatment significantly lowers 24-hour systolic blood pressure but not diastolic blood pressure, as compared with inactive acupoint treatment. Furthermore, distinctive changes are observed between the metabolomics data of the two groups. Multivariate analysis shows that only in the active acupoint treatment group can the follow-up plasma be clearly separated from the baseline plasma. Moreover, the follow-up plasma of these two groups can be clearly separated, indicating two different post-treatment metabolic phenotypes. Three metabolites, sucrose, cellobiose, and hypoxanthine, are shown to be the most important features of active acupoint treatment. This study demonstrates that metabolomic analysis is a potential tool that can be used to efficiently differentiate the effect of active acupoints from inactive acupoints in treating hypertension. Possible mechanisms are the alternation of hypothalamic microinflammation and the restoration of host-gut microbiota interactions induced by acupuncture.

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“…However, the precise mechanisms by which CIH induces activation of neurons in the PVN and increases sympathetic nerve activity are incompletely understood. New evidence reveals that excessive oxidative stress and inflammation in the cardiovascular regulatory centers of the brain, particularly in the PVN, lead to neuronal activation and augmented sympathetic nerve activity in various forms of hypertension and other cardiovascular diseases ( Dange et al, 2015 ; Shen et al, 2015 ; Khor and Cai, 2017 ; Li Y. et al, 2017 ; Haspula and Clark, 2018 ; Jiang et al, 2018 ; Zhang et al, 2018 ). Microglia, the resident immune cells in the central nervous system, are often the major sources of pro-inflammatory cytokines in the central nervous system ( Kiernan et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the PVN has been shown to increase sympathetic nerve activity and blood pressure in rats exposed to CIH ( Knight et al, 2011 ; Sharpe et al, 2013 ). Accumulating evidence indicates that oxidative stress and inflammation in the PVN are major contributors to the augmented sympathetic nerve activity in various forms of hypertension and other cardiovascular diseases ( Dange et al, 2015 ; Khor and Cai, 2017 ; Haspula and Clark, 2018 ; Jiang et al, 2018 ; Zhang et al, 2018 ). A recent study has demonstrated that CIH causes elevated oxidative stress and inflammation in the brain regions associated with neurodegeneration ( Snyder et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Elevated Oxidative Stress and Inflammation in Hypothalamic Paraventricular Nucleus Are Associated With Sympathetic Excitation and Hypertension in Rats Exposed to Chronic Intermittent Hypoxia

Yan-li

Gua

et al. 2018

Front. Physiol.

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Obstructive sleep apnea (OSA), characterized by recurrent collapse of the upper airway during sleep leading to chronic intermittent hypoxia (CIH), is an independent risk factor for hypertension. Sympathetic excitation has been shown to play a major role in the pathogenesis of OSA-associated hypertension. Accumulating evidence indicates that oxidative stress and inflammation in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center, mediate sympathetic excitation in many cardiovascular diseases. Here we tested the hypothesis that CIH elevates oxidative stress and inflammation in the PVN, which might be associated with sympathetic excitation and increased blood pressure in a rat model of CIH that mimics the oxygen profile in patients with OSA. Sprague-Dawley rats were pretreated with intracerebroventricular (ICV) infusion of vehicle or superoxide scavenger tempol, and then exposed to control or CIH for 7 days. Compared with control+vehicle rats, CIH+vehicle rats exhibited increased blood pressure, and increased sympathetic drive as indicated by the blood pressure response to ganglionic blockade and plasma norepinephrine levels. Pretreatment with ICV tempol prevented CIH-induced increases in blood pressure and sympathetic drive. Molecular studies revealed that expression of NAD(P)H oxidase subunits, production of reactive oxygen species, expression of proinflammatory cytokines and neuronal excitation in the PVN were elevated in CIH+vehicle rats, compared with control+vehicle rats, but were normalized or reduced in CIH rat pretreated with ICV tempol. Notably, CIH+vehicle rats also had increased systemic oxidative stress and inflammation, which were not altered by ICV tempol. The results suggest that CIH induces elevated oxidative stress and inflammation in the PVN, which lead to PVN neuronal excitation and are associated with sympathetic excitation and increased blood pressure. Central oxidative stress and inflammation may be novel targets for the prevention and treatment of hypertension in patients with OSA.

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Hypothalamic and inflammatory basis of hypertension

Cited by 33 publications

References 176 publications

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

Active Acupoints Differ from Inactive Acupoints in Modulating Key Plasmatic Metabolites of Hypertension: A Targeted Metabolomics Study

Elevated Oxidative Stress and Inflammation in Hypothalamic Paraventricular Nucleus Are Associated With Sympathetic Excitation and Hypertension in Rats Exposed to Chronic Intermittent Hypoxia

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