Potentiation of vasoconstriction and pressor response by low concentration of monomethylarsonous acid (MMAIII)

Kyung Min Lim, Yoo Sun Shin, Seojin Kang, Ji Yoon Noh, Keunyoung Kim, Seung Min Chung, Yeo Pyo Yun, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 (MMAIII), a toxic trivalent methylated arsenic metabolite, can potentiate agonist-induced vasoconstriction and pressor responses. In freshly isolated rat aortic ring, exposure to nanomolar MMAIII (100-500nM) potentiated phenylephrine (PE)-induced vasoconstriction while at higher concentrations (≥2.5μM), 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 MMAIII 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, MMAIII enhanced agonist-induced activation of small GTPase RhoA, a key contributor to Ca2+ sensitization. Of note, treatment of MMAIII 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 MMAIII may shed light on arsenic-associated hypertension.

Original languageEnglish
Pages (from-to)250-256
Number of pages7
JournalToxicology Letters
Volume205
Issue number3
DOIs
StatePublished - 10 Sep 2011

Bibliographical note

Funding Information:
This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 20100016038 ).

Keywords

  • Arsenic
  • Cardiovascular toxicity
  • Monomethylarsonous acid
  • Vasoconstriction

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