Visualization of Spatially-Controlled Vasospasm by Sympathetic Nerve-Mediated ROCK Activation.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
03
04
2020
revised:
06
09
2020
accepted:
23
09
2020
pubmed:
19
10
2020
medline:
23
1
2021
entrez:
18
10
2020
Statut:
ppublish
Résumé
Contraction of vascular smooth muscle is regulated primarily by calcium concentration and secondarily by ROCK activity within the cells. In contrast to the wealth of information regarding regulation of calcium concentration, little is known about the spatiotemporal regulation of ROCK activity in live blood vessels. Here, we report ROCK activation in subcutaneous arterioles in a transgenic mouse line that expresses a genetically encoded ROCK biosensor based on the principle of Fӧrster resonance energy transfer by two-photon excitation in vivo imaging. Rapid vasospasm was induced upon laser ablation of arterioles, concomitant with a transient increase in calcium concentration in arteriolar smooth muscles. Unlike the increase in calcium concentration, vasoconstriction and ROCK activation continued for several minutes after irradiation. Both the ROCK inhibitor, fasudil, and the ganglionic nicotinic acetylcholine receptor blocker, hexamethonium, inhibited laser-induced ROCK activation and reduced the duration of vasospasm at the segments distant from the irradiated point. These observations suggest that vasoconstriction is initially triggered by a rapid surge of cytoplasmic calcium and then maintained by sympathetic nerve-mediated ROCK activation.
Identifiants
pubmed: 33069718
pii: S0002-9440(20)30459-4
doi: 10.1016/j.ajpath.2020.09.012
pii:
doi:
Substances chimiques
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
194-203Informations de copyright
Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.