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J Pharmacol Exp Ther ; 328(1): 223-30, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18955588

RESUMO

Occupational exposure to hand-operated vibrating tools causes a spectrum of pathological changes in the vascular, neurological, and musculoskeletal systems described as the hand-arm vibration syndrome (HAVS). Experiments were performed to determine the effects of acute vibration on the function of digital arteries. Rats paws were exposed to a vibrating platform (4 h, 125 Hz, constant acceleration of 49 m/s(2) root mean squared), and digital artery function was assessed subsequently in vitro using a pressure myograph system. Constriction to phenylephrine or 5-hydroxytryptamine was reduced in digital arteries from vibrated paws. However, after endothelium denudation, constriction to the agonists was no longer impaired in vibrated arteries. Inhibition of nitric-oxide synthase (NOS) with N(omega)-nitro-l-arginine methyl ester (l-NAME) increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. However, nitric oxide (NO) activity, determined using the NO-sensitive probe 4-amino-5-methylamino-2', 7'-difluorofluorescein, was reduced in vibrated compared with control arteries. Endogenous levels of reactive oxygen species (ROS), determined using the ROS-sensitive probe 5-(and 6)-chloromethyl-2',7'-dichlorodihydro-fluorescein, were increased in vibrated compared with control arteries. The increased ROS levels were abolished by L-NAME or by catalase, which degrades extracellular hydrogen peroxide. Catalase also increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. The results suggest that acute vibration causes vascular dysfunction in digital arteries by increasing ROS levels, which is probably mediated by uncoupling of endothelial NOS. Therefore, therapeutic strategies to inhibit ROS or augment NO activity may be beneficial in HAVS.


Assuntos
Síndrome da Vibração do Segmento Mão-Braço/fisiopatologia , Fenilefrina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Serotonina/uso terapêutico , Vibração/efeitos adversos , Animais , Artérias/efeitos dos fármacos , Artérias/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Dedos/irrigação sanguínea , Síndrome da Vibração do Segmento Mão-Braço/prevenção & controle , Humanos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Restrição Física , Vasoconstrição/efeitos dos fármacos
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