Repositorio
Institucional

Palacios, Javier

Cifuentes, Fredi#Paredes, Adrian#Nwokocha, Chukwuemeka R.#Paz, Cristian

8-Oxo-9-Dihydromakomakine Isolated from Aristotelia chilensis Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx

MDPI

MOLECULES

en

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE, 10(-6) M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10(-4) M) significantly reduced the contractile response to KCl (p < 0.001) more than PE (p < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10(-4) M) drastically reduced the contraction to KCl (610(-2) M), but after that, PE (10(-6) M) caused contraction (p < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10(-5) M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker, TEA, 5 x 10(-3) M, p < 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker, 5 x 10(-3) M, p < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10(-5) M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase, 10(-3) M, p < 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844, 10(-8) M, p < 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies.

Artículo original

This research was supported by the grant [DI17-0049] from the Universidad de La Frontera, Chile and Network for Extreme Environments Research project (NEXER, Project [ANT1756], Universidad de Antofagasta, Chile).

Esta investigación fue financiada por la beca [DI17-0049] de la Universidad de La Frontera, Chile y el proyecto Red de Investigación en Ambientes Extremos (NEXER, Proyecto [ANT1756], Universidad de Antofagasta, Chile).

10.3390/molecules23113050

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Aristotelia chilensis Molina Stuntz# vascular activity# endothelium-independent# indole alkaloid# 8-oxo-9-dihydromakomakine# voltage-dependent calcium channels

http://dx.doi.org/10.3390/molecules23113050

Biochemistry & Molecular Biology# Chemistry, Multidisciplinary

Aristotelia chilensis Molina Stuntz# actividad vascular# independiente del endotelio# alcaloide indol# 8-oxo-9-dihidromakomaquina# canales de calcio dependientes de voltaje

Farmacología y Farmacia

Fisiología

Sistema Cardiovascular y Cardiaco

version publicada

dorada

verde

acceso abierto

acceso abierto

WOS:000451641900322

8-Oxo-9-Dihydromakomakine Isolated from <i>Aristotelia chilensis</i> Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx

Artículo original

MDPI

MOLECULES

Bioquímica y Biología Molecular# Química, Multidisciplinar

en

UFRO DI17-0049#UA ANT1756

UFRO DI17-0049

NEXER

Universidad de Antofagasta ANT1756

This research was supported by the grant [DI17-0049] from the Universidad de La Frontera, Chile and Network for Extreme Environments Research project (NEXER, Project [ANT1756], Universidad de Antofagasta, Chile).

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CC BY

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