Inorganic arsenite potentiates vasoconstriction through calcium sensitization in vascular smooth muscle

Moo Yeol Lee, Young Ho Lee, Kyung Min Lim, Seung Min Chung, Ok Nam Bae, Heon Kim, Choong Ryeol Lee, Jung Duck Park, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested - arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) - arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca2+ measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K+ without concomitant increase in intracellular Ca2+ elevation, suggesting that, rather than direct Ca2+ elevation, Ca2+ sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these in vitro results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels.

Original languageEnglish
Pages (from-to)1330-1335
Number of pages6
JournalEnvironmental Health Perspectives
Volume113
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Arsenic
  • Arsenite
  • Blood vessels
  • Calcium sensitization
  • Cardiovascular disease
  • Myosin light chain phosphorylation
  • Vasoconstriction

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