Niclosamide ethanolamine inhibits artery constriction

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Mitochondrial Biology

Background:

• Mitochondrial uncouplers like CCCP can inhibit artery constriction.
• Niclosamide ethanolamine (NEN) is an FDA-approved drug known to uncouple mitochondrial oxidative phosphorylation.

Purpose of the Study:

• To investigate the vasoactivity of NEN and its underlying mechanisms.
• To determine if NEN could be a potential anti-hypertensive agent.

Main Methods:

• Isometric tension recordings in rat mesenteric arteries and thoracic aorta using a multi-wire myograph system.
• Western blot analysis to measure protein levels.
• Assessment of cellular ADP/ATP ratio, AMPK activation, and cytosolic calcium levels.
• Experiments using AMPKα1 knockout mice and SERCA inhibitors.

Main Results:

• NEN demonstrated vasorelaxant effects, inhibiting phenylephrine- and high K+-induced artery constriction.
• NEN increased cellular ADP/ATP ratio and activated AMP-activated protein kinase (AMPK) in vascular smooth muscle cells and aorta.
• NEN-induced vasodilation was attenuated in AMPKα1 knockout mice and by SERCA inhibitors, but not KATP channel blockers.
• NEN increased cytosolic calcium and depolarized mitochondrial membrane potential.

Conclusions:

• Niclosamide ethanolamine (NEN) exhibits significant vasorelaxant properties.
• NEN's mechanism involves mitochondrial uncoupling, AMPK activation, and modulation of intracellular calcium levels.
• NEN shows promise as an anti-hypertensive drug, but potential vasodilation-related side effects warrant consideration.