Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle

By Lee, Moo-Yeol; Lee, Young-Ho et al. | Environmental Health Perspectives, October 2005 | Go to article overview

Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle


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


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 (MM[A.sup.V]), and dimethylarsinic acid (DM[A.sup.V])--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 [Ca.sup.2+] measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high [K.sup.+] without concomitant increase in intracellular [Ca.sup.2+] elevation, suggesting that, rather than direct [Ca.sup.2+] elevation, [Ca.sup.2+] 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. Key words: arsenic, arsenite, blood vessels, calcium sensitization, cardiovascular disease, myosin light chain phosphorylation, vasoconstriction. Environ Health Perspect 113:1330-1335 (2005). doi: 10.1289/ehp.8000 available via http://dx.doi.org/[Online 14 June 2005]

**********

Arsenic is a ubiquitous element distributed in the environment, and millions of people are chronically exposed to arsenic worldwide (Abernathy et al. 1999). Naturally contaminated drinking water is the main source of arsenic exposure, posing potential risk to human health (Nordstrom 2002; Schoen et al. 2004; Smith et al. 2002). Chronic arsenic exposure has been associated with a wide range of illnesses including cancer, hyperkeratosis, diabetes, and cardiovascular disease (Engel et al. 1994; Rossman 2003; Tseng 2004; Yu et al. 1984). Cardiovascular effects of arsenic exposure include hypertension, atherosclerosis, cerebrovascular disease, ischemic heart disease, and peripheral vascular disorders such as black-foot disease (resulting from gangrene caused by obstruction of peripheral blood vessels) in humans (Chen et al. 1995, 1996; Chiou et al. 1997; Rahman et al. 1999; Simeonova et al. 2003; Wang et al. 2002).

Lee et al. (2002) recently suggested that the mechanism for arsenic-induced cardiovascular disease is the increased susceptibility of platelets to aggregate, resulting in enhanced arterial thrombosis. Other mechanisms may also be responsible for the diversity of human cardiovascular disease from chronic arsenic exposure. One possibility is that arsenic may alter the normal vasomotor tone of blood vessels, which rises from contractility of vascular smooth muscle cells.

The contraction of smooth muscle is regulated by mediators such as neural and humoral factors, mechanical forces, and vasoactive substances from endothelial cells. Vascular smooth muscle contraction is triggered primarily by a rise in intracellular free [Ca.sup.2+] concentration (Sanders 2001). [Ca.sup.2+] binds to calmodulin (CAM), allowing [Ca.sup.2+]--CaM complex formation, which binds to and activates myosin light chain kinase (MLCK) (Horowitz et al. 1996). The active MLCK catalyzes the phosphorylation of the regulatory myosin light chain (MLC), which then triggers myosin--actin interaction, leading to the shortening of muscle and generation of force. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

    Already a member? Log in now.