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Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries
Xiyue Zhang1,2, Xinzi Zhang1,2, Yanqiu Zhang1,2
1Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China.
Abstract:
Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca2+]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca2+]i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.
Insights
Triclosan, an antibacterial agent, causes vasodilation by uncoupling mitochondria in vascular smooth muscle cells. This effect relaxes constricted rat arteries, suggesting potential vasodilation if absorbed excessively in vivo.
Area of Science:
- Vascular Biology
- Mitochondrial Physiology
- Pharmacology
Background:
- Mitochondrial uncouplers are known to induce vasodilation.
- Triclosan, a common antibacterial agent, has been reported to induce mitochondrial uncoupling.
Purpose of the Study:
- To investigate the effects of triclosan on vascular function in rat mesenteric arteries and aorta.
- To determine the mechanism by which triclosan affects vascular smooth muscle cells.
Main Methods:
- Isometric tension recordings using a multi-wire myograph system.
- Measurement of cytosolic calcium ([Ca2+]i), mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential in A10 cells using laser scanning confocal microscopy.
Main Results:
- Triclosan treatment relaxed phenylephrine- and high K+-induced constriction in both rat mesenteric arteries and aorta.
- Triclosan induced vasorelaxation without activating KATP channels.
- Triclosan increased cytosolic [Ca2+]i, enhanced mitoROS production, and depolarized mitochondrial membrane potential in A10 cells.
Conclusions:
- Triclosan induces mitochondrial uncoupling in vascular smooth muscle cells.
- Triclosan effectively relaxes constricted rat mesenteric arteries and aorta.
- Excessive in vivo absorption of triclosan may lead to vasodilation.
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