HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMA III): a contributing factor to arsenic-associated cardiovascular diseases.

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 (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.
AuthorsOk-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
JournalEnvironmental research (Environ Res) Vol. 108 Issue 3 Pg. 300-8 (Nov 2008) ISSN: 1096-0953 [Electronic] Netherlands
PMID18701095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium Channels, L-Type
  • Organometallic Compounds
  • Reactive Oxygen Species
  • monomethylarsonous acid
  • L-Lactate Dehydrogenase
  • Arsenic
  • Calcium
Topics
  • Animals
  • Arsenic (toxicity)
  • Calcium (metabolism)
  • Calcium Channels, L-Type (metabolism)
  • Cardiovascular Diseases (chemically induced, etiology)
  • L-Lactate Dehydrogenase (metabolism)
  • Male
  • Muscle, Smooth, Vascular (drug effects, physiopathology)
  • Organometallic Compounds (toxicity)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (metabolism)
  • Vasoconstriction (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: