Atractyloside induces low contractile reaction of arteriolar smooth muscle through mitochondrial damage.

Rui Song, Huining Bian, Xuliang Huang, Ke-seng Zhao

Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou, People's Republic of China.

Journal of applied toxicology : JAT 2012 Jun

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Atractyloside is the principal naturally occurring active ingredient in ethnomedicines and animal grazing forage. Evidence that atractyloside can induce opening of the mitochondrial permeability transition pore (mPTP) indicates that mitochondrial mechanisms may play an important role in pathophysiological lesions of the heart, liver and kidney after atractyloside poisoning. Therefore, in this study we investigated the association of atractyloside-induced mitochondrial damage in arteriolar smooth muscle cells (ASMCs) with contractile reaction. Atractyloside led to depolarized and swollen or damaged ASMC mitochondria, which might be related to the concentration-dependent induction of mPTP opening. Relative ATP content in ASMCs was significantly reduced by 48%, 63% and 66% of control when cells were treated with 7.5, 10, and 15 µm atractyloside for 10 min, respectively, and ASMCs were hyperpolarized. In addition, the contractile responsiveness of ASMCs was eventually weakened. These results suggest that atractyloside has a toxic effect on vasoreactivity, which is possibly related to mitochondrial damage. Copyright © 2011 John Wiley & Sons, Ltd.

Citation

Rui Song, Huining Bian, Xuliang Huang, Ke-seng Zhao. Atractyloside induces low contractile reaction of arteriolar smooth muscle through mitochondrial damage. Journal of applied toxicology : JAT. 2012 Jun;32(6):402-8