Vascular distribution of nanomaterials

Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

doi:10.1002/wnan.1271

Cited by 48 publications

(19 citation statements)

References 53 publications

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“…This differential effect on vascular smooth muscle response in the macrocirculation may be caused by the turbulent flow patterns characteristic of this segment, which contribute to an increased likelihood of deposition and impaction of ENM agglomerates particularly at large artery bifurcations (39). …”

Section: Discussionmentioning

confidence: 99%

Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

Abukabda

Stapleton

McBride

et al. 2017

Front. Cardiovasc. Med.

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A growing body of research links engineered nanomaterial (ENM) exposure to adverse cardiovascular endpoints. The purpose of this study was to evaluate the impact of ENM exposure on vascular reactivity in discrete segments so that we may determine the most sensitive levels of the vasculature where these negative cardiovascular effects are manifest. We hypothesized that acute nano-TiO2 exposure differentially affects reactivity with a more robust impairment in the microcirculation. Sprague-Dawley rats (8–10 weeks) were exposed to nano-TiO2 via intratracheal instillation (20, 100, or 200 µg suspended per 250 µL of vehicle) 24 h prior to vascular assessments. A serial assessment across distinct compartments of the vascular tree was then conducted. Wire myography was used to evaluate macrovascular active tension generation specifically in the thoracic aorta, the femoral artery, and third-order mesenteric arterioles. Pressure myography was used to determine vascular reactivity in fourth- and fifth-order mesenteric arterioles. Vessels were treated with phenylephrine, acetylcholine (ACh), and sodium nitroprusside. Nano-TiO2 exposure decreased endothelium-dependent relaxation in the thoracic aorta and femoral arteries assessed via ACh by 53.96 ± 11.6 and 25.08 ± 6.36%, respectively. Relaxation of third-order mesenteric arterioles was impaired by 100 and 20 µg nano-TiO2 exposures with mean reductions of 50.12 ± 8.7 and 68.28 ± 8.7%. Cholinergic reactivity of fourth- and fifth-order mesenteric arterioles was negatively affected by nano-TiO2 with diminished dilations of 82.86 ± 12.6% after exposure to 200 µg nano-TiO2, 42.6 ± 12.6% after 100 µg nano-TiO2, and 49.4 ± 12.6% after 20 µg nano-TiO2. Endothelium-independent relaxation was impaired in the thoracic aorta by 34.05 ± 25% induced by exposure to 200 µg nano-TiO2 and a reduction in response of 49.31 ± 25% caused by 100 µg nano-TiO2. Femoral artery response was reduced by 18 ± 5%, while third-order mesenteric arterioles were negatively affected by 20 µg nano-TiO2 with a mean decrease in response of 38.37 ± 10%. This is the first study to directly compare the differential effect of ENM exposure on discrete anatomical segments of the vascular tree. Pulmonary ENM exposure produced macrovascular and microvascular dysfunction resulting in impaired responses to endothelium-dependent, endothelium-independent, and adrenergic agonists with a more robust dysfunction at the microvascular level. These results provide additional evidence of an endothelium-dependent and endothelium-independent impairment in vascular reactivity.

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Section: Discussionmentioning

confidence: 99%

Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

Abukabda

Stapleton

McBride

et al. 2017

Front. Cardiovasc. Med.

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“…For example, the above speculation may be accurate; however, the possibility of direct particle interaction within the vasculature cannot be overlooked (Stapleton and Nurkiewicz, 2014b). In this instance nanomaterial translocation to the uterine vasculature, albeit a small fraction compared to injection or pulmonary deposition, (Sumner et al, 2015; Stapleton et al, 2012a) may act as a pro-oxidant, quenching local NO bioavailability and initiating an inflammatory signaling cascade, leading to increased uterine venular leukocyte activity.…”

Section: Discussionmentioning

confidence: 99%

Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

Stapleton

McBride

et al. 2015

Toxicology and Applied Pharmacology

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With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m3, 5 h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10−4 M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated.

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“…Following the uptake of intact and degraded substances through epithelial cells to the underlying lymph fluid, they can either remain there, circulate in the lymph fluid through lymphatic ducts that eventually drain into the systemic cardiovascular circulatory system, or be absorbed directly into capillaries of the cardiovascular circulatory system . Buccal cavity and esophageal capillaries lead into systemic veins, whereas capillaries from the stomach and intestines pass through the liver before entering systemic circulation . A portion of absorbed substances can thereby be secreted back into the intestinal lumen via enterohepatic circulation through the gallbladder in bile.…”

Section: Gi Tract Anatomy Mediating the Absorption Of Nmsmentioning

confidence: 99%

Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food‐relevant nanomaterials

Bellmann

Carlander²,

Fasano

et al. 2015

WIREs Nanomed Nanobiotechnol

110

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Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding of the stability of these entities in the GI lumen, and an understanding of whether or not they can be absorbed and thus become systemically available. Data are emerging on the mammalian in vivo absorption of engineered NMs composed of chemicals with a range of properties, including metal, mineral, biochemical macromolecules, and lipid‐based entities. In vitro and in silico fluid incubation data has also provided some evidence of changes in particle stability, aggregation, and surface properties following interaction with luminal factors present in the GI tract. The variables include physical forces, osmotic concentration, pH, digestive enzymes, other food, and endogenous biochemicals, and commensal microbes. Further research is required to fill remaining data gaps on the effects of these parameters on NM integrity, physicochemical properties, and GI absorption. Knowledge of the most influential luminal parameters will be essential when developing models of the GI tract to quantify the percent absorption of food‐relevant engineered NMs for risk assessment. WIREs Nanomed Nanobiotechnol 2015, 7:609–622. doi: 10.1002/wnan.1333For further resources related to this article, please visit the WIREs website.

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Vascular distribution of nanomaterials

Cited by 48 publications

References 53 publications

Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food‐relevant nanomaterials

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