Acetylcholine released by endothelial cells facilitates flow-mediated dilatation

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Circulating blood generates frictional forces (shear-stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow-mediated dilatation. Whilst some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing acetylcholine. Once liberated, acetylcholine acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow-activated release of acetylcholine from the endothelium is non-vesicular and occurs via organic cation transporters. Acetylcholine is generated following mitochondrial production of acetylCoA. Thus, we show acetylcholine is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.
LanguageEnglish
Pages7267-7307
Number of pages41
JournalJournal of Physiology
Volume594
Issue number24
Early online date12 Oct 2016
DOIs
Publication statusPublished - 14 Dec 2016

Fingerprint

Acetylcholine
Dilatation
Endothelial Cells
Endothelium
Blood Vessels
Arteries
Autocrine Communication
Vasodilator Agents
Smooth Muscle Myocytes
Neurotransmitter Agents
Cations
Nitric Oxide
Calcium

Keywords

  • endothelium
  • calcium
  • flow-mediated dilation
  • acetylcholine
  • endothelial calcium signalling
  • autocrine signalling molecules
  • endothelial mechanotransduction

Cite this

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abstract = "Circulating blood generates frictional forces (shear-stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow-mediated dilatation. Whilst some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing acetylcholine. Once liberated, acetylcholine acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow-activated release of acetylcholine from the endothelium is non-vesicular and occurs via organic cation transporters. Acetylcholine is generated following mitochondrial production of acetylCoA. Thus, we show acetylcholine is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.",
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Acetylcholine released by endothelial cells facilitates flow-mediated dilatation. / Wilson, Calum; Lee, Matthew D.; McCarron, John G.

In: Journal of Physiology, Vol. 594, No. 24, 14.12.2016, p. 7267-7307.

Research output: Contribution to journalArticle

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AU - Wilson, Calum

AU - Lee, Matthew D.

AU - McCarron, John G.

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N2 - Circulating blood generates frictional forces (shear-stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow-mediated dilatation. Whilst some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing acetylcholine. Once liberated, acetylcholine acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow-activated release of acetylcholine from the endothelium is non-vesicular and occurs via organic cation transporters. Acetylcholine is generated following mitochondrial production of acetylCoA. Thus, we show acetylcholine is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.

AB - Circulating blood generates frictional forces (shear-stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow-mediated dilatation. Whilst some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing acetylcholine. Once liberated, acetylcholine acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow-activated release of acetylcholine from the endothelium is non-vesicular and occurs via organic cation transporters. Acetylcholine is generated following mitochondrial production of acetylCoA. Thus, we show acetylcholine is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.

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KW - calcium

KW - flow-mediated dilation

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