TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans.
Acrolein
/ analogs & derivatives
Cyclooxygenase Inhibitors
/ pharmacology
Humans
Nitric Oxide
/ metabolism
Nitric Oxide Synthase
/ metabolism
Prostaglandin-Endoperoxide Synthases
/ metabolism
Skin
Sweating
TRPA1 Cation Channel
Transient Receptor Potential Channels
/ pharmacology
Vasodilation
Young Adult
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
received:
22
07
2021
accepted:
06
11
2021
pubmed:
6
1
2022
medline:
30
4
2022
entrez:
5
1
2022
Statut:
ppublish
Résumé
Transient receptor potential ankyrin 1 (TRPA1) channel activation induces cutaneous vasodilation in humans in vivo. However, the mechanisms underlying this response remains equivocal. We hypothesized that nitric oxide synthase (NOS) and Ca2+ activated K+ (KCa) channels contribute to the TRPA1 channel-induced cutaneous vasodilation with no involvement of cyclooxygenase (COX). Cutaneous vascular conductance (CVC) in 9 healthy young adults was assessed at 4 dorsal forearm skin sites treated by intradermal microdialysis with (1) 1.985% dimethyl sulfoxide + 0.015% lactated Ringer solution with propylene glycol (vehicle control), (2) 10 mM l-NAME, a nonselective NOS inhibitor, (3) 10 mM ketorolac, a nonselective COX inhibitor, or (4) 50 mM tetraethylammonium, a nonselective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose-dependent manner (2.9%, 8.8%, 26%, and 80%, each lasting ≥30 minutes). Administration of ≥8.8% cinnamaldehyde increased CVC from baseline at the vehicle control site by as much as 27.4% (95% confidence interval of 5.3; P < 0.001). NOS inhibitor attenuated the cinnamaldehyde-induced increases in CVC at the 8.8%, 26%, and 80% concentrations relative to the vehicle control site (all P ≤ 0.05). In contrast, both the COX inhibitor and KCa channel blockers did not attenuate the cinnamaldehyde induced-increases in CVC relative to the vehicle control site for all concentrations (all P ≥ 0.130). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with no detectable contributions of COX and KCa channels.
Identifiants
pubmed: 34983913
doi: 10.1097/FJC.0000000000001188
pii: 00005344-202203000-00016
doi:
Substances chimiques
Cyclooxygenase Inhibitors
0
TRPA1 Cation Channel
0
TRPA1 protein, human
0
Transient Receptor Potential Channels
0
Nitric Oxide
31C4KY9ESH
Acrolein
7864XYD3JJ
Nitric Oxide Synthase
EC 1.14.13.39
Prostaglandin-Endoperoxide Synthases
EC 1.14.99.1
cinnamaldehyde
SR60A3XG0F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
375-382Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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