Brain stem oxidative stress and its associated signaling in the regulation of sympathetic vasomotor tone

2012 ◽  
Vol 113 (12) ◽  
pp. 1921-1928 ◽  
Author(s):  
Samuel H. H. Chan ◽  
Julie Y. H. Chan
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Brain Stem ◽  
Ventrolateral Medulla ◽  
Future Research ◽  
Vasomotor Tone ◽  
Cellular Mechanisms ◽  
Neurogenic Hypertension ◽  
The Impact ◽  
Sympathetic Vasomotor Tone

There is now compelling evidence from studies in humans and animals that overexcitation of the sympathetic nervous system plays an important role in the pathogenesis of cardiovascular diseases. An excellent example is neurogenic hypertension, in which central sympathetic overactivation is involved in the development, staging, and progression of the disease, and one of the underlying mechanisms involves oxidative stress in key brain stem sites that are engaged in the regulation of sympathetic vasomotor tone. Using the rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) as two illustrative brain stem neural substrates, this article provides an overview of the impact of reactive oxygen species and antioxidants on RVLM and NTS in the pathogenesis of neurogenic hypertension. This is followed by a discussion of the redox-sensitive signaling pathways, including several kinases, ion channels, and transcription factors that underpin the augmentation in sympathetic vasomotor tone. In addition, the emerging view that brain stem oxidative stress is also causally related to a reduction in sympathetic vasomotor tone and hypotension during brain stem death, methamphetamine intoxication, and temporal lobe status epilepticus will be presented, along with the causal contribution of the oxidant peroxynitrite formed by a reaction between nitric oxide synthase II (NOS II)-derived nitric oxide and superoxide. Also discussed as a reasonable future research direction is dissection of the cellular mechanisms and signaling cascades that may underlie the contributory role of nitric oxide generated by different NOS isoforms in the differential effects of oxidative stress in the RVLM or NTS on sympathetic vasomotor tone.

Mercury Exposure and Endothelial Dysfunction

2015 ◽  
Vol 34 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Swati Omanwar ◽  
M. Fahim
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelium ◽  
Circulatory System ◽  
Vital Role ◽  
Mercury Exposure ◽  
And Function ◽  
The Impact ◽  
And Oxidative Stress

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

Abstract 814: Atorvastatin Attenuates Oxidative Stress And Improves Neuronal Nitric Oxide Synthase In The Brain Stem Of Heart Failure Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Joseph Francis ◽  
Li Yu ◽  
Anuradha Guggilam ◽  
Srinivas Sriramula ◽  
Irving H Zucker
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Brain Stem ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Neuronal Nos ◽  
The Brain

3-Hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the incidence of myocardial infarction independent of their lipid-lowering effects. Nitric oxide (NO) in the central nervous system contributes to cardiovascular regulatory mechanisms. Imbalance between nitric oxide (NO) and superoxide anion (O 2 . − ) in the brain may contribute to enhanced sympathetic drive in heart failure (HF). This study was done to determine whether treatment with atorvastatin (ATS) ameliorates the imbalance between NO and O 2 . − production in the brain stem and contributes to improvement of left ventricular (LV) function. Methods and Results: Myocardial infarction (MI) was induced by ligation of the left coronary artery or sham surgery. Subsequently, mice were treated with ATS (10 μg/kg) (MI + ATS), or vehicle (MI + V). After 5 weeks, echocardiography revealed left ventricular dilatation in MI mice. Realtime RT-PCR indicated an increase in the mRNA expression of the LV hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Neuronal NOS (nNOS) and endothelial NOS (eNOS) mRNA expression were significantly reduced, while that of NAD(P)H oxidase subunit (gp91phox) expression was elevated in the brain stem of MI mice. Compared with sham-operated mice, ATS-treated mice showed reduced cardiac dilatation, decreased ANP and BNP in the LV. ATS also reduced gp91phox expression and increased nNOS mRNA expression in the brain stem, while no changes in eNOS and iNOS were observed. Conclusion: These findings suggest that ATS reduces oxidative stress and increases neuronal NOS in the brain stem, and improves left ventricular function in heart failure.

scholarly journals Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons

2004 ◽  
Vol 96 (2) ◽  
pp. 784-791 ◽  
Author(s):  
Jay B. Dean ◽  
Daniel K. Mulkey ◽  
Richard A. Henderson ◽  
Stephanie J. Potter ◽  
Robert W. Putnam
Keyword(s):  
Oxidative Stress ◽  
Brain Stem ◽  
Brain Slices ◽  
Respiratory Control ◽  
In Vivo Studies ◽  
Future Research ◽  
Direct Effects ◽  
Underlying Assumption

Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.

Inhibitory Vasomotor Neurons in the Caudal Ventrolateral Medulla Oblongata

Physiology ◽  
1991 ◽  
Vol 6 (3) ◽  
pp. 139-141 ◽  
Author(s):  
WW Blessing
Keyword(s):  
Medulla Oblongata ◽  
Gabaergic Neurons ◽  
Ventrolateral Medulla ◽  
Vasomotor Tone ◽  
Caudal Ventrolateral Medulla ◽  
Premotor Neurons ◽  
Sympathetic Vasomotor Tone

Tonically active, probably GABAergic, neurons in the caudal ventrolateral medulla oblongata decrease sympathetic vasomotor tone by directly inhibiting sympathoexcitatory premotor neurons in the rostral medulla. These caudal inhibitory vasomotor neurons may constitute the inhibitory link in the central baroreceptor-vasomotor pathway.

Contribution to sympathetic vasomotor tone of tonic glutamatergic inputs to neurons in the RVLM

2004 ◽  
Vol 287 (6) ◽  
pp. R1335-R1343 ◽  
Author(s):  
Jouji Horiuchi ◽  
Suzanne Killinger ◽  
Roger A. L. Dampney
Keyword(s):  
Excitatory Amino Acid ◽  
Ventrolateral Medulla ◽  
Tonic Activity ◽  
Vasomotor Tone ◽  
Renal Sympathetic Nerve Activity ◽  
Vehicle Injection ◽  
Sympathetic Vasomotor Tone ◽  
Modest Reduction ◽  
Renal Sympathetic

The role of excitatory amino acid (EAA) receptors in the rostral ventrolateral medulla (RVLM) in maintaining resting sympathetic vasomotor tone remains unclear. It has been proposed that EAA receptors in the RVLM mediate excitatory inputs both to presympathetic neurons and to interneurons in the caudal ventrolateral medulla (CVLM), which then provide a counterbalancing inhibition of RVLM presympathetic neurons. In this study, we tested this hypothesis by determining the effect of blockade of EAA receptors in the RVLM on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), after inhibition of CVLM neurons. In anesthetized rats, bilateral injections of muscimol in the CVLM increased MAP, HR, and RSNA. Subsequent bilateral injections of kynurenic acid (Kyn, 2.7 nmol) in the RVLM caused a modest reduction of ∼20 mmHg in the MAP but had no effect, when compared with the effect of vehicle injection alone, on HR or RSNA. By ∼50 min after the injections of Kyn or vehicle in the RVLM, the MAP had stabilized at a level close to its original baseline level, but the HR and RSNA stabilized at levels above baseline. The results indicate that removal of tonic EAA drive to RVLM neurons has little effect on the tonic activity of RVLM presympathetic neurons, even when inputs from the CVLM are blocked. Thus the tonic activity of RVLM presympathetic neurons under these conditions is dependent on excitatory synaptic inputs mediated by non-EAA receptors and/or the autoactivity of these neurons.

scholarly journals Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review

2014 ◽  
Vol 25 (6) ◽  
Author(s):  
Lauren E. Salminen ◽  
Robert H. Paul
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Future Research ◽  
Aging Brain ◽  
Older Individuals ◽  
Glutathione S Transferase ◽  
Antioxidant Defense Enzymes ◽  
Repair Mechanisms ◽  
The Impact ◽  
The Brain

AbstractNormal aging involves a gradual breakdown of physiological processes that leads to a decline in cognitive functions and brain integrity, yet the onset and progression of decline are variable among older individuals. While many biological changes may contribute to this degree of variability, oxidative stress is a key mechanism of the aging process that can cause direct damage to cellular architecture within the brain. Oligodendrocytes are at a high risk for oxidative damage due to their role in myelin maintenance and production and limited repair mechanisms, suggesting that white matter may be particularly vulnerable to oxidative activity. Antioxidant defense enzymes within the brain, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), are crucial for breaking down the harmful end products of oxidative phosphorylation. Previous studies have revealed that allele variations of polymorphisms that encode these antioxidants are associated with abnormalities in SOD, CAT, GPx, and GST activity in the central nervous system. This review will focus on the role of oxidative stress in the aging brain and the impact of decreased antioxidant defense on brain integrity and cognitive function. Directions for future research investigations of antioxidant defense genes will also be discussed.

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