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-5methylamino- 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'-dichlorodihydrofluorescein, 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.
Nicholas A. Flavahan, Johns Hopkins University, School of Medicine, Department of Anesthesiology & Critocal Care Medicine, Ross Res Bldg, Room 370, 720 Rutland Ave, Baltimore, MD 21205
CODEN
JPETAB
CAS No.
10102-43-9
Publication Date
20090101
Document Type
Journal Article
Email Address
nflavah1@jhmi.edu
Fiscal Year
2009
Issue of Publication
1
ISSN
0022-3565
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Journal of Pharmacology and Experimental Therapeutics
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