Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways

Knuckles, Travis L.; Yi, Jinghai; Frazer, David G.; Leonard, Howard D.; Chen, Bean T.; Castranova, Vince; Nurkiewicz, Timothy R.

doi:10.3109/17435390.2011.606926

Cited by 64 publications

(73 citation statements)

References 61 publications

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“…29 Similar microvascular dysfunction has been reported after inhalation of nano-titanium dioxide and has been associated with stimulation of sensory neurons from the lung and enhanced sympathetic input at the systemic arterioles. 30,31 Aspiration of MWCNTs has also been reported to increase baroreflex activity in rats. 32,33 In addition, Erdely et al 34 reported transient elevation of blood inflammatory mediators after aspiration of MWCNTs, which may mediate this systemic microvascular response.…”

Section: Cardiovascular Responsesmentioning

confidence: 99%

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

2012

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CONSPECTUSCarbon nanotubes (CNTs) are carbon atoms arranged in a crystalline graphene lattice with a tubular morphology. CNTs exhibit high tensile strength, possess unique electrical properties, are durable, and can be functionalized. These properties allow applications as structural materials, in electronics, as heating elements, in batteries, in the production of stain-resistant fabric, for bone grafting and dental implants, and for targeted drug delivery. Carbon nanofibers (CNFs) are strong, flexible fibers that are currently used to produce composite materials.Agitation can lead to aerosolized CNTs and CNFs, and peak airborne particulate concentrations are associated with workplace activities such as weighing, transferring, mixing, blending, or sonication. Most airborne CNTs or CNFs found in workplaces are loose agglomerates of micrometer diameter. However, due to their low density, they linger in workplace air for a considerable time, and a large fraction of these structures are respirable.In rat and mouse models, pulmonary exposure to single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), or CNFs causes the following pulmonary reactions: acute pulmonary inflammation and injury, rapid and persistent formation of granulomatous lesions at deposition sites of large CNT agglomerates, and rapid and progressive alveolar interstitial fibrosis at deposition sites of more dispersed CNT or CNF structures.Pulmonary exposure to SWCNTs can induce oxidant stress in aortic tissue and increases plaque formation in an atherosclerotic mouse model. Pulmonary exposure to MWCNTs depresses the ability of coronary arterioles to respond to dilators. These cardiovascular effects may result from neurogenic signals from sensory irritant receptors in the lung. Pulmonary exposure to MWCNTs also upregulates mRNA for inflammatory mediators in selected brain regions, and pulmonary exposure to SWCNTs upregulates the baroreceptor reflex. In addition, pulmonary exposure to MWCNTs may induce levels of inflammatory mediators in the blood, which may affect the cardiovascular system.

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Section: Cardiovascular Responsesmentioning

confidence: 99%

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

2012

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“…Maintaining the appropriate environmental parameters inside the chamber is insufficient if the concentration of test compound varies from location to location 3 . The nanoparticle concentrations were measured at four different locations in the zones just above the cages in the exposure chamber.…”

Section: Uniformity Of Distributionmentioning

confidence: 99%

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Chen

Schwegler‐Berry

et al. 2013

JoVE

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Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σ g < 2.5 5 . The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size 6 , which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria 5 .A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO 2 inhalation toxicology studies. Critical components: 1) novel nano-TiO 2 aerosol generator; 2) 0.5 m 3 whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO 2 aerosols generated from bulk dry nano-TiO 2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm 3 ) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m /min), and t is the sampling time (minute). The chamber pressure, temperature, relative humidity (RH), O 2 and CO 2 concentrations were monitored and controlled continuously. Nano-TiO 2 aerosols collected on Nuclepore filters were analyzed with a scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analysis.In summary, we report that the nano-particle aerosols generated and delivered to our exposure chamber have: 1) steady mass concentration; 2) homogenous composition free of contaminants; 3) stable particle size distributions with a count-median aerodynamic diameter of 157 nm during aerosol generation. This system reliably and repeatedly creates test atmospheres that simulate occupational, environmental or domestic ENM aerosol exposures. Video LinkThe video component of this article can be found at http://www.jove.com/video/50263/ ProtocolThe whole-body nanoparticle inhalation exposure step-by-step operating procedures are described as follows.Note: 1) steps 1 and 3 should be performed in a fume hood; 2) operators must wear appropriate personal protective equipment (respirators, goggles and rubber gloves).

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“…Whereas studies of neurological dysfunction impairing the resistance vasculature remain limited, our work has indicated that inhalation of titanium dioxide nanoparticles leads to a perturbation of physiologic alpha-adrenergic receptor sensitivity, inducing a persistent, sympathetically mediated arteriolar dysfunction (68). Because maintenance of systemic blood pressure is largely influenced by peripheral vascular resistance, the need to evaluate the resistance vasculature directly becomes evident.…”

Section: Cardiovascular Outcomesmentioning

confidence: 96%

Xenobiotic pulmonary exposure and systemic cardiovascular response via neurological links

Stapleton

Abukabda

Hardy

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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The cardiovascular response to xenobiotic particle exposure has been increasingly studied over the last two decades, producing an extraordinary scope and depth of research findings. With the flourishing of nanotechnology, the term "xenobiotic particles" has expanded to encompass not only air pollution particulate matter (PM) but also anthropogenic particles, such as engineered nanomaterials (ENMs). Historically, the majority of research in these fields has focused on pulmonary exposure and the adverse physiological effects associated with a host inflammatory response or direct particle-tissue interactions. Because these hypotheses can neither account entirely for the deleterious cardiovascular effects of xenobiotic particle exposure nor their time course, the case for substantial neurological involvement is apparent. Indeed, considerable evidence suggests that not only is neural involvement a significant contributor but also a reality that needs to be investigated more thoroughly when assessing xenobiotic particle toxicities. Therefore, the scope of this review is several-fold. First, we provide a brief overview of the major anatomical components of the central and peripheral nervous systems, giving consideration to the potential biologic targets affected by inhaled particles. Second, the autonomic arcs and mechanisms that may be involved are reviewed. Third, the cardiovascular outcomes following neurological responses are discussed. Lastly, unique problems, future risks, and hurdles associated with xenobiotic particle exposure are discussed. A better understanding of these neural issues may facilitate research that in conjunction with existing research, will ultimately prevent the untoward cardiovascular outcomes associated with PM exposures and/or identify safe ENMs for the advancement of human health.

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Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways

Cited by 64 publications

References 61 publications

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Xenobiotic pulmonary exposure and systemic cardiovascular response via neurological links

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