3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F24%3A10486494" target="_blank" >RIV/00216208:11160/24:10486494 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xGlI6He2e1" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xGlI6He2e1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.vph.2024.107418" target="_blank" >10.1016/j.vph.2024.107418</a>

Jazyk výsledku

angličtina

Název v původním jazyce

3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study

Popis výsledku v původním jazyce

Some substituted catechols are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. In this current study, we aimed at testing of 22 chemically-related catechols in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tertbutylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC(50)s ranging from similar to 10 to 24 microM. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. Activation of voltage-gated potassium channels (K-V) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the K(V)7.4 channel.

Název v anglickém jazyce

3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study

Popis výsledku anglicky

Some substituted catechols are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. In this current study, we aimed at testing of 22 chemically-related catechols in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tertbutylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC(50)s ranging from similar to 10 to 24 microM. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. Activation of voltage-gated potassium channels (K-V) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the K(V)7.4 channel.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/NU21-02-00135" target="_blank" >NU21-02-00135: Kardiovaskulární účinky flavonoidních metabolitů a vliv metabolických rizikových faktorů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Vascular Pharmacology

ISSN

1537-1891

e-ISSN

1879-3649

Svazek periodika

156

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

107418

Kód UT WoS článku

001302807400001

EID výsledku v databázi Scopus

2-s2.0-85201899406