Niclosamide ethanolamine inhibits artery constriction
| Autor: | Zhi-Jie Sun, Nan Hu, Yu Tai, Jing Jin, Yan-Qiu Zhang, Shan-Liang Li, Ming-Yu Liu, Jie Yan, Xiaolin Xiao, Jin-Lai Gao, Chang-Lin Zhen, Xin Shen, De-Li Dong, Xin-Zi Zhang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Vascular smooth muscle Vasodilator Agents Myocytes Smooth Muscle Aorta Thoracic Vasodilation AMP-Activated Protein Kinases Pharmacology Muscle Smooth Vascular Rats Sprague-Dawley Mice Phenylephrine 03 medical and health sciences chemistry.chemical_compound KATP Channels medicine.artery medicine Animals Thoracic aorta Ethanolamine Vascular Diseases Mesenteric arteries Antihypertensive Agents Aorta Niclosamide Chemistry Mesenteric Arteries Rats Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Vasoconstriction cardiovascular system Cyclopiazonic acid Myograph medicine.drug |
| Zdroj: | Pharmacological Research. 115:78-86 |
| ISSN: | 1043-6618 |
| Popis: | We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect