Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation

Wu, Kay L H; Chan, Samuel H.H.; Chan, Julie Y.H.

doi:10.1186/1742-2094-9-212

Cited by 159 publications

(154 citation statements)

References 64 publications

(103 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…Studies investigating the underlying pathophysiology of hypertension indicates the involvement of neuroimmune interactions. Chronic systemic inflammation causes neurogenic hypertension mediated through neuroinflammation and oxidative stress in the rostral ventrolateral medulla [221]. Overexpression of junctional adhesion molecule-1 leads to leukocyte adherence to microvasculature, resulting in hypertension in previously normotensive rats [222].…”

Section: Hypertensionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

View full text Add to dashboard Cite

Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

show abstract

Section: Hypertensionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

View full text Add to dashboard Cite

show abstract

“…Oxidative stress in the brain plays an important role in the development of hypertension (103,231,239). Nox-induced ROS production in the rostral ventrolateral medulla causes sympathoexcitation in hypertensive rats, through mechanisms that involve NO and pro-inflammatory processes.…”

Section: Oxidative Stress and Experimental Hypertensionmentioning

confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

232

177

View full text Add to dashboard Cite

Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

show abstract

“…Superoxide measurements were performed in duplicate according to previously published methods (21,48). Briefly, ϳ1.5 ϫ 10 6 cells were incubated with 5 M dihydroethidium (DHE; Life Technologies) and drug or control (PBS only) treatments in a final volume of 300 l of serum-free PBS for 60 min at 37°C.…”

Section: Detection Of Intracellular Superoxide Levelsmentioning

confidence: 99%

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Deo

Jenkins

Padilla

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Deo SH, Jenkins NT, Padilla J, Parrish AR, Fadel PJ. Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via ␣-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 305: R1124 -R1132, 2013. First published September 25, 2013 doi:10.1152/ajpregu.00347.2013.-Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter norepinephrine (NE) increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. After NE (50 pg/ml, 50 ng/ml, and 50 g/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91 phox , p22 phox , and p67 phox ) was assessed using realtime RT-PCR, and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14ϩ monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time-dependent manner (superoxide: 0.9 Ϯ 0.2 fold, 6 h vs. 3.0 Ϯ 0.3 fold, 36 h; NE, 50 g/ml; P Ͻ 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via ␣-adrenergic receptors, preferentially ␣ 2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor Staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14ϩ monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through ␣-adrenergic receptors, an effect facilitating monocyte adhesion to the endothelium. sympathetic nerve activity; reactive oxygen species; oxidative stress CHRONICALLY ELEVATED SYMPATHETIC NERVE ACTIVITY is a hallmark characteristic of several cardiovascular diseases (14,17,29). Recently, many of these diseases have also been shown to exhibit elevated systemic oxidative stress (9,19,38). However, it is unclear whether elevated oxidative stress causes sympathoexcitation or vice versa.Numerous studies performed in animals have convincingly shown that an increase in central superoxide levels induces activation of key brain areas, such as the rostral ventrolateral medulla, to cause sympathoexcitation (4,33,44,53,54). In contrast, to our knowledge, little consideration has been given to the potential ability of the sympathetic neurotransmitter norepinephrine (NE) to increase oxidative stress. In...

show abstract

Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation

Cited by 159 publications

References 64 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors

Contact Info

Product

Resources

About