Source:http://linkedlifedata.com/resource/pubmed/id/21708234
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2011-8-2
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| pubmed:abstractText |
A close link between arsenic exposure and hypertension has been well-established through many epidemiological reports, yet the mechanism underlying it remains unclear. Here we report that nanomolar concentrations of monomethylarsonous acid (MMA(III)), a toxic trivalent methylated arsenic metabolite, can potentiate agonist-induced vasoconstriction and pressor responses. In freshly isolated rat aortic ring, exposure to nanomolar MMA(III) (100-500 nM) potentiated phenylephrine (PE)-induced vasoconstriction while at higher concentrations (?2.5 ?M), suppression of vasoconstriction and apoptosis of vascular smooth muscle were observed. Potentiation of agonist-induced vasoconstriction was also observed with other contractile agonists and it was retained in endothelium-denuded aortic rings, suggesting that these events are agonist-independent and smooth muscle cell dependent. Interestingly, exposure to MMA(III) resulted in increased myosin light chain phosphorylation while PE-induced Ca2+ influx was not affected, reflecting that Ca2+ sensitization is involved. In line with this, MMA(III) enhanced agonist-induced activation of small GTPase RhoA, a key contributor to Ca2+ sensitization. Of note, treatment of MMA(III) to rats induced significantly higher pressor responses in vivo, demonstrating that this event can occur in vivo indeed. We believe that RhoA-mediated Ca2+ sensitization and the resultant potentiation of vasoconstriction by MMA(III) may shed light on arsenic-associated hypertension.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arsenicals,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/monomethylarsonous acid,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1879-3169
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011. Published by Elsevier Ireland Ltd.
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| pubmed:issnType |
Electronic
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| pubmed:day |
10
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| pubmed:volume |
205
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
250-6
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| pubmed:meshHeading |
pubmed-meshheading:21708234-Animals,
pubmed-meshheading:21708234-Aorta, Thoracic,
pubmed-meshheading:21708234-Apoptosis,
pubmed-meshheading:21708234-Arsenic Poisoning,
pubmed-meshheading:21708234-Arsenicals,
pubmed-meshheading:21708234-Calcium Signaling,
pubmed-meshheading:21708234-Cells, Cultured,
pubmed-meshheading:21708234-Enzyme Activation,
pubmed-meshheading:21708234-Hypertension,
pubmed-meshheading:21708234-Male,
pubmed-meshheading:21708234-Muscle, Smooth, Vascular,
pubmed-meshheading:21708234-Myosin Light Chains,
pubmed-meshheading:21708234-Organometallic Compounds,
pubmed-meshheading:21708234-Osmolar Concentration,
pubmed-meshheading:21708234-Phosphorylation,
pubmed-meshheading:21708234-Pressoreceptors,
pubmed-meshheading:21708234-Rats,
pubmed-meshheading:21708234-Rats, Sprague-Dawley,
pubmed-meshheading:21708234-Vasoconstriction,
pubmed-meshheading:21708234-Vasoconstrictor Agents,
pubmed-meshheading:21708234-rhoA GTP-Binding Protein
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| pubmed:year |
2011
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| pubmed:articleTitle |
Potentiation of vasoconstriction and pressor response by low concentration of monomethylarsonous acid (MMA(III)).
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| pubmed:affiliation |
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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