NAD(P)H oxidase inhibiting with apocynin improved vascular reactivity in tail-suspended hindlimb unweighting rat

Zhang, Ran; Ran, Hong; Ma, Jing; Bai, Yuxiang; Lin, Lejian

doi:10.1007/s13105-011-0123-1

Cited by 32 publications

(31 citation statements)

References 21 publications

(41 reference statements)

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“…However, this latter finding contradicts a reported increase in NO following apocynin 47, 48 . It is possible that the relatively short time allowed after acute apocynin administration in our study accounts for such discrepancy because NO decreases and increases following acute (minutes) and extended (hours/days) exposure to apocynin 49 .…”

Section: Discussionmentioning

confidence: 82%

Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-mediated Pressor Response in Conscious Rats

McGee

Abdel‐Rahman

2014

Journal of Cardiovascular Pharmacology

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The molecular mechanisms for peripheral N-Methyl-D-Aspartate receptor (NMDAR)-mediated vascular oxidative stress and pressor response are not known. We conducted integrative (in vivo) and ex vivo biochemical studies to test the hypothesis that ROS-dependent calcium influx, triggered by activation of vascular kinases, underlies the NMDAR-mediated pressor response. Pharmacological inhibition of PI3K/Akt (Wortmannin; 15 μg/kg), PKC (Chelerythrine; 5 mg/kg, i.v.), Ca2+ influx (nifedipine; 0.35 or 0.75 mg/kg) or NOX (apocynin; 5 mg/kg) attenuated the peripheral NMDAR-mediated pressor response in conscious male Sprague-Dawley rats. NMDAR activation enhanced the phosphorylation of Akt, ERK1, JNK and p38 (Western blot) and NADPH oxidase (NOX) activity in vascular tissues collected during the pressor response caused by NMDA infusion (180 μg/kg/min, 30 min). Further, ex vivo studies showed that wortmannin, chelerythrine or apocynin abrogated the NMDAR-mediated vascular NO and ROS generation and NOX activation in the vasculature. These findings implicate vascular PI3K/Akt-PKC signaling in the peripheral NMDAR-mediated increases in vascular NO and NOX activation (ROS), which ultimately lead to calcium influx and pressor response in conscious rats.

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Section: Discussionmentioning

confidence: 82%

Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-mediated Pressor Response in Conscious Rats

McGee

Abdel‐Rahman

2014

Journal of Cardiovascular Pharmacology

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“…Studies have also shown that changes in NADPH oxidase expression can mediate radiation-induced oxidative stress in rat brain microvascular endothelial cells (56). Furthermore, a recent study demonstrated that NADPH oxidase-derived oxidative stress mediated abnormal vascular reactivity in hindlimb unloaded rats (21). FIG.…”

Section: Simulated Spaceflight Induces Oxidative Damage In Brainmentioning

confidence: 97%

“…Studies have shown that both microgravity encountered by astronauts in space, as well as modeled microgravity on Earth, can induce many deleterious physiological effects including changes in brain structure and function (20). As with radiation, one of the mechanisms involved in the response to spaceflight is oxidative stress (21,22). Studies have shown that exposure to microgravity during space flights is associated with increased oxidative stress markers reflecting damage to lipids, including lipid peroxidation, in the brain of both humans and rodents (23,24).…”

Section: Introductionmentioning

confidence: 99%

Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain

et al. 2016

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Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence that prolonged exposure to simulated microgravity and LDR radiation is associated with increased oxidative stress biomarkers that may increase the likelihood of brain injury and reduced antioxidant defense. NOX2-containing nicotinamide adenosine dinucleotide phosphate (NADPH oxidase) may contribute to spaceflight environment-induced oxidative stress.

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“…of the upper body region, whereas there are atrophic adaptations and reduced contractile responsiveness in arteries of the lower body region (Tuday et al 2007;Lin et al 2009;Zhang et al 2012;Behnke et al 2013;Taylor et al 2013). For the large and elastic conduit arteries, it is reported that simulated microgravity induced an increase in blood pressure and flow in the common carotid artery of rats (Zhang 2013).…”

Section: Vascular Remodeling During Real/simulated Microgravitymentioning

confidence: 99%

“…We have previously demonstrated that simulated microgravity induced hypertrophic changes and increased the expression levels of ROS and VCAM-1 in the common carotid artery of rats (Zhang et al 2008(Zhang et al , 2009. We have also reported that simulated microgravity activated the angiotensin II (Ang II)/angiotensin type 1 receptor (AT1) signaling pathway and induced the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived oxidative stress in the common carotid artery of rats (Zhang et al 2012), all of which suggested that there may be an inflammatory response in the common carotid artery of rats exposed to simulated microgravity.…”

Section: Vascular Remodeling During Real/simulated Microgravitymentioning

confidence: 99%

Simulated microgravity induces an inflammatory response in the common carotid artery of rats

Liu

Wang

Yuan

et al. 2014

Can. J. Physiol. Pharmacol.

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Post-spaceflight orthostatic intolerance is one of the most important adverse effects after exposure to space microgravity, and there are still no effective countermeasures. It has been considered that arterial remodeling may play an important role in the occurrence of post-spaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. In this study, we investigated whether an inflammatory response exists in the common carotid artery of rats exposed to simulated microgravity. For this, Sprague-Dawley rats were subjected to 4 weeks of hindlimb unweighting to simulate microgravity. The expression levels of the adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1), and the cytokine monocyte chemoattractant protein-1 (MCP-1) in the common carotid artery of simulated microgravity rats were evaluated by immunohistochemical staining, quantitative RT-PCR, and Western blot analyses. The recruitment of monocytes in the common carotid artery of rats exposed to simulated microgravity was investigated by en face immunofluorescence staining and monocyte binding assays. Our results provided convincing evidence that there is an inflammatory response in the common carotid artery of rats exposed to simulated microgravity. Our work suggests that the inflammatory response may be a novel cellular mechanism that is responsible for the arterial remodeling that occurs during exposure to microgravity.

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NAD(P)H oxidase inhibiting with apocynin improved vascular reactivity in tail-suspended hindlimb unweighting rat

Cited by 32 publications

References 21 publications

Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-mediated Pressor Response in Conscious Rats

Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-mediated Pressor Response in Conscious Rats

Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain

Simulated microgravity induces an inflammatory response in the common carotid artery of rats

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