Whole-Body Nanoparticle Aerosol Inhalation Exposures

Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle ...

West Virginia University 

The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 Î¼g lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness.

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

L&#39;augmentation g&eacute;n&eacute;ralis&eacute;e de la production et l&#39;utilisation des nanomat&eacute;riaux a augment&eacute; le risque d&#39;exposition des nanoparticules ; Cependant, les effets biologiques des nanoparticules par inhalation sont mal compris. Des rats ont &eacute;t&eacute; expos&eacute;s aux a&eacute;rosols de taille nano dioxyde de titane (charge de poumons 10 &mu;g) ; en prophylaxie post-exposition de 24h, le muscle de spinotrapezius a &eacute;t&eacute; pr&eacute;par&eacute; pour la microscopie intravitale. Exposition de nanoparticules n&#39;a pas alt&eacute;r&eacute; la stimulation des nerfs p&eacute;rivasculaires (PVNS)-induite par une constriction art&eacute;riolaire dans des conditions normales ; Cependant, l&#39;inhibition des r&eacute;cepteurs adr&eacute;nergiques a r&eacute;v&eacute;l&eacute; un effet plus robuste. Inhalation de nanoparticules r&eacute;duit la dilatation art&eacute;riolaire en r&eacute;ponse &agrave; une hyper&eacute;mie active (AH). Dans les exp&eacute;riences de PVNS et de AH, inhibition de l&#39;oxyde nitrique synthase (NOS) affect&eacute; uniquement des contr&ocirc;les. Alors que l&#39;inhibition des cyclooxyg&eacute;nases (COX) att&eacute;nu&eacute;e seulement dilatation art&eacute;riolaire AH-induite chez les animaux expos&eacute;s de nanoparticules. Ce groupe affiche une renforc&eacute;e U46619 constriction et att&eacute;nu&eacute;e iloprost induite par la dilatation. Collectivement, ces &eacute;tudes indiquent que l&#39;exposition de nanoparticules r&eacute;duit microvasculaire non biodisponibilit&eacute; et alt&egrave;re la vasor&eacute;activit&eacute; induite par COX. En outre, la sensibilit&eacute; accrue des r&eacute;cepteurs adr&eacute;nergiques sugg&egrave;re une r&eacute;activit&eacute; sympathique augment&eacute;e.

Inhalation de nanoparticules modifie une vasor&eacute;activit&eacute; art&eacute;riolaire syst&eacute;mique par des voies sympathiques et induite par la cyclo-oxyg&eacute;nase.

Il diffuso aumento nella produzione e nell&#39;utilizzo dei nanomateriali &egrave; aumentato il potenziale per l&#39;esposizione alle nanoparticelle; Tuttavia, gli effetti biologici di inalazione delle nanoparticelle sono capiti male. Ratti erano esposti agli aerosol di biossido di titanio di dimensioni nanometriche (onere del polmone 10 &mu;g); a post-esposizione di 24 h, il muscolo spinotrapezius &egrave; stato preparato per microscopia intravital. L&#39;esposizione delle nanoparticelle non alterava perivascolare stimolazione nervosa (PVNS)-indotta da costrizione arteriolare in condizioni normali; Tuttavia, l&#39;inibizione del recettore adrenergico ha rivelato un effetto pi&ugrave; robusto. Inalazione delle nanoparticelle ridotta dilatazione arteriolare in risposta a iperemia attiva (AH). In esperimenti sia PVNS e AH, ossido nitrico sintasi (NOS) inibizione colpiti solo i controlli. Considerando che l&#39;inibizione cyclooxygenase (COX) attenuato solo dilatazione arteriolare AH-indotte negli animali esposti delle nanoparticelle. Questo gruppo visualizzato un&#39;avanzata U46619 costrizione e dilatazione indotta da iloprost attenuato. Collettivamente, questi studi indicano che l&#39;esposizione delle nanoparticelle riduce NO microvascolare biodisponibilit&agrave; e altera vasoreactivity COX-mediata. Inoltre, la sensibilit&agrave; del recettore adrenergico avanzata suggerisce un&#39;aumentata reattivit&agrave; simpatica.

Inalazione delle nanoparticelle altera vasoreactivity arteriolare sistemico attraverso percorsi simpatici e cyclooxygenase-mediata.

OBJECTIVE: The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. While the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding "special" circulations is the enhanced maternal system to support fetal development. The "Barker Hypothesis" proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was two-fold: 1) to determine if maternal ENM exposure alters uterine and/or fetal microvascular function and 2) test the Barker Hypothesis at the microvascular level. STUDY DESIGN: Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3Â±0.039 (mg/m(3))/hour, 5 hours/day, 8.2Â±0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (<150Î¼m passive diameter) of the uterine premyometrial and fetal tail arteries were conducted. RESULTS: ENM exposures led to significant maternal and fetal microvascular dysfunction which presented as robustly compromised endothelium-dependent and -independent reactivity to pharmacologic and mechanical stimuli. Isolated maternal uterine arteriolar reactivity was consistent with a metabolically impaired profile and hostile gestational environment, impacting fetal weight. The fetal microvessels isolated from exposed dams demonstrate significant impairments to signals of vasodilation specific to mechanistic signaling and shear stress. CONCLUSION: To our knowledge, this is the first report providing evidence that maternal ENM inhalation is capable of influencing fetal health, thereby supporting that the Barker Hypothesis is applicable at the microvascular level.

Maternal Engineered Nanomaterial Exposure and Fetal Microvascular Function: Does the Barker Hypothesis Apply?

OBJECTIF : Le d&eacute;veloppement et l&#39;utilisation des nanomat&eacute;riaux (manufactur&eacute;s ENM) a donn&eacute; lieu &agrave; des pr&eacute;occupations sur la possibilit&eacute; d&#39;effets sur la sant&eacute; humaine. Alors que la compr&eacute;hension de la toxicit&eacute; cardiovasculaire du ENM s&#39;am&eacute;liore, l&#39;un des plus complexes et aigu&euml; exigeant des circulations &laquo; sp&eacute;ciales &raquo; est le syst&egrave;me maternels am&eacute;lior&eacute; pour soutenir le d&eacute;veloppement du foetus. Le &laquo; hypoth&egrave;se de Barker &raquo; propose que le d&eacute;veloppement du foetus au sein d&#39;un environnement hostile gestationnel peut pr&eacute;disposer/programme future sensibilit&eacute;. Par cons&eacute;quent, l&#39;objectif de cette &eacute;tude &eacute;tait double: 1) pour d&eacute;terminer si une exposition maternelle ENM alt&egrave;re fonction microvasculaire ut&eacute;rine et/ou foetale et 2) v&eacute;rifier l&#39;hypoth&egrave;se de Barker au niveau microvasculaire. CONCEPTION de l&#39;&eacute;tude : Enceinte rats Sprague-Dawley (10 jours de gestation) ont &eacute;t&eacute; expos&eacute;s &agrave; des a&eacute;rosols de nano-titanium dioxyde (11.3&plusmn;0.039 (mg/m(3)) / 5 heures/jour, heure, 8.2&plusmn;0.85 jours) d&#39;&eacute;valuer les cons&eacute;quences microvasculaires foetus et maternels de l&#39;exposition de la m&egrave;re. Isolement de tissu microvasculaire (20e jour de gestation) et &eacute;tudes de r&eacute;activit&eacute; art&eacute;riolaire (&lt; 150&mu;m diam&egrave;tre passive) des premyometrial ut&eacute;rin et queue foetale art&egrave;res ont &eacute;t&eacute; men&eacute;es. R&Eacute;SULTATS : Expositions ENM conduit &agrave; la dysfonction microvasculaire foetale et maternelle importante, qui pr&eacute;sente comme robuste compromise r&eacute;activit&eacute; ind&eacute;pendante et endoth&eacute;lium-d&eacute;pendante aux stimuli m&eacute;caniques et pharmacologiques. Isol&eacute; de la r&eacute;activit&eacute; art&eacute;riolaire ut&eacute;rine maternelle &eacute;tait conforme &agrave; un profil m&eacute;tabolique avec facult&eacute;s affaiblie et gestationnel hostiles, ayant une incidence sur le poids f&oelig;tal. Les microvaisseaux f&oelig;tales isol&eacute;es de m&egrave;res expos&eacute;es montrent des d&eacute;ficiences importantes aux signaux de vasodilatation sp&eacute;cifique m&eacute;caniste de la signalisation et la contrainte de cisaillement. CONCLUSION: &Agrave; notre connaissance, c&#39;est le premier rapport prouvant que ENM maternelle inhalation est capable d&#39;influencer la sant&eacute; f&oelig;tale, soutenant ainsi que l&#39;hypoth&egrave;se de Barker s&#39;applique au niveau microvasculaire.

Maternelle d&#39;ing&eacute;nierie nanomat&eacute;riau exposition et fonction microvasculaire foetale : l&#39;hypoth&egrave;se de Barker s&#39;applique-t-elle ?

OBIETTIVO: Il costante sviluppo e utilizzo dei nanomateriali ingegnerizzati (ENM) ha suscitato preoccupazioni sopra il potenziale di effetti sulla salute umana. Mentre sta migliorando la comprensione della tossicit&agrave; cardiovascolare di ENM, uno dei pi&ugrave; complessi ed esigenti acutamente circolazioni &quot;speciale&quot; &egrave; il sistema materno avanzato per sostenere lo sviluppo del feto. il &quot;ipotesi Barker&quot; propone che lo sviluppo del feto all&#39;interno di un ambiente ostile gestazionale pu&ograve; predisporre/programma futuro sensibilit&agrave;. Pertanto, l&#39;obiettivo di questo studio &egrave; stato duplice: 1) per determinare se esposizione materna ENM altera la funzione microvascolare uterina e/o fetale e 2) testare l&#39;ipotesi di Barker a livello microvascolare. STUDIO di progettazione: Incinta ratti Sprague-Dawley (giorno di gestazione 10) erano esposti agli aerosol di nano-titanio biossido (11.3&plusmn;0.039 (mg/m(3)) / ora, 5 ore al giorno, 8.2&plusmn;0.85 giorni) per valutare le conseguenze materne e fetali microvascolare di esposizione materna. Isolamento dei tessuti Microvascolari (giorno di gestazione 20) e studi di reattivit&agrave; arteriolare (&lt; 150&mu;m passivo diametro) del premyometrial uterini e feto coda sono state condotte le arterie. RISULTATI: Le esposizioni ENM ha portato a significativa materna e feto disfunzione microvascolare che presentato come robustamente compromessa endotelio-dipendente e - indipendente reattivit&agrave; agli stimoli meccanici e farmacologiche. Reattivit&agrave; arteriolare uterina materna isolato era coerente con il profilo metabolicamente compromessa e ostile ambiente gestazionale, un impatto peso fetale. La talengectasia fetale isolato da dighe esposte dimostra significative menomazioni ai segnali di vasodilatazione specifica segnalazione meccanicistico e shear stress. CONCLUSIONE: A nostra conoscenza, questo &egrave; il primo rapporto fornendo prove che materna ENM inalazione &egrave; in grado di influenzare la salute fetale, sostenendo in tal modo che l&#39;ipotesi di Barker &egrave; applicabile a livello microvascolare.

Jinghai Yi

Department of Physiology and Pharmacology,
School of Medicine,
Center for Cardiovascular and Respiratory Sciences,
Department of Physiology and Pharmacology, School of Medicine

West Virginia University

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Jinghai Yi

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Physiology and Pharmacology,School of Medicine,Center for Cardiovascular and Respiratory Sciences,Department of Physiology and Pharmacology, School of Medicine

West Virginia University

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Department of Physiology and Pharmacology,
School of Medicine,
Center for Cardiovascular and Respiratory Sciences,
Department of Physiology and Pharmacology, School of Medicine