Linked Life Data

18701095

Source:http://linkedlifedata.com/resource/pubmed/id/18701095

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-10-28
pubmed:abstractText
While arsenic in drinking water is known to cause various cardiovascular diseases in human, exact mechanism still remains elusive. Recently, trivalent-methylated arsenicals, the metabolites of inorganic arsenic, were shown to have higher cytotoxic potential than inorganic arsenic. To study the role of these metabolites in arsenic-induced cardiovascular diseases, we investigated the effect of monomethylarsonous acid (MMA III), a major trivalent-methylated arsenical, on vasomotor tone of blood vessels. In isolated rat thoracic aorta and small mesenteric arteries, MMA III irreversibly suppressed normal vasoconstriction induced by three distinct agonists of phenylephrine (PE), serotonin and endothelin-1. Inhibition of vasoconstriction was retained in aortic rings without endothelium, suggesting that MMA III directly impaired the contractile function of vascular smooth muscle. The effect of MMA III was mediated by inhibition of PE-induced Ca2+ increase as found in confocal microscopy and fluorimeter in-lined organ chamber technique. The attenuation of Ca2+ increase was from concomitant inhibition of release from intracellular store and extracellular Ca2+ influx via L-type Ca2+ channel, which was blocked by MMA III as shown in voltage-clamp assay in Xenopus oocytes. MMA III did not affect downstream process of Ca2+, as shown in permeabilized arterial strips. In in vivo rat model, MMA III attenuated PE-induced blood pressure increase indeed, supporting the clinical relevance of these in vitro findings. In conclusion, MMA III-induced smooth muscle dysfunction through disturbance of Ca2+ regulation, which results in impaired vasoconstriction and aberrant blood pressure change. This study will provide a new insight into the role of trivalent-methylated arsenicals in arsenic-associated cardiovascular diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-0953
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
300-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMA III): a contributing factor to arsenic-associated cardiovascular diseases.
pubmed:affiliation
College of Pharmacy, Seoul National University, Shinrim-dong San 56-1, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't