Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMAIII): A contributing factor to arsenic-associated cardiovascular diseases

Ok Nam Bae, Eun Kyung Lim, Kyung Min Lim, Ji Yoon Noh, Seung Min Chung, Moo Yeol Lee, Yeo Pyo Yun, Seong Chun Kwon, Jun Ho Lee, Seung Yeol Nah, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 (MMAIII), a major trivalent-methylated arsenical, on vasomotor tone of blood vessels. In isolated rat thoracic aorta and small mesenteric arteries, MMAIII 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 MMAIII directly impaired the contractile function of vascular smooth muscle. The effect of MMAIII 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 MMAIII as shown in voltage-clamp assay in Xenopus oocytes. MMAIII did not affect downstream process of Ca2+, as shown in permeabilized arterial strips. In in vivo rat model, MMAIII attenuated PE-induced blood pressure increase indeed, supporting the clinical relevance of these in vitro findings. In conclusion, MMAIII-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.

Original languageEnglish
Pages (from-to)300-308
Number of pages9
JournalEnvironmental Research
Volume108
Issue number3
DOIs
StatePublished - Nov 2008

Keywords

  • Arsenic
  • Cardiovascular diseases
  • Monomethylarsonous acid (MMA)
  • Smooth muscle dysfunction
  • Vasoconstriction

Fingerprint

Dive into the research topics of 'Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMAIII): A contributing factor to arsenic-associated cardiovascular diseases'. Together they form a unique fingerprint.

Cite this