Study summary · research use only
Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this rat study using isolated mesenteric arteries and A10 vascular smooth muscle cells, the authors report that the mitochondrial uncoupler BAM15 relaxed and inhibited phenylephrine-induced constriction of arteries with and without intact endothelium. BAM15 showed an IC50 for vasorelaxation comparable to that of CCCP and niclosamide, but was less cytotoxic to A10 cells than either. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial reactive oxygen species production, and increased mitochondrial oxygen consumption rate. BAM15 activated AMPK in A10 cells with greater potency than CCCP, niclosamide, and the AMPK activators metformin and AICAR.
Abstract
Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC50 value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.
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