Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta
Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. <i>Aristotelia chilensis</i> (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated t...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-07-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/24/15/2748 |
id |
doaj-337e9b69b88b4ffdb1f98828ebf156c5 |
---|---|
record_format |
Article |
spelling |
doaj-337e9b69b88b4ffdb1f98828ebf156c52020-11-24T21:34:29ZengMDPI AGMolecules1420-30492019-07-012415274810.3390/molecules24152748molecules24152748Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat AortaFernando Romero0Javier Palacios1Ignacio Jofré2Cristian Paz3Chukwuemeka R. Nwokocha4Adrián Paredes5Fredi Cifuentes6Vicerrectoría de Investigación y Postgrado, Programa de Doctorado en Ciencias Médicas, Universidad de la Frontera, Temuco 4780000, ChileLaboratorio de Bioquímica Aplicada, Departamento de Química y Farmacia, Facultad Ciencias de la Salud, Universidad Arturo Prat, Iquique 1110939, ChileLaboratorio de Neurociencias y Biología de Péptidos, Centro de Excelencia en Biotecnología de La Reproducción, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, ChileLaboratorio de Productos Naturales y Descubrimiento de Fármacos, Departamento de Ciencias básicas, Universidad de La Frontera, Temuco 4811230, ChileDepartment of Basic Medical Sciences Physiology Section, Faculty of Medical Sciences, The University of the West Indies, Mona, Kingston 7, KGN, Jamaica (W.I.)Laboratorio de Química Biológica, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1270300, ChileLaboratorio de Fisiología Experimental, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1270300, ChileAlkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. <i>Aristotelia chilensis</i> (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl<sub>2</sub> (Kir), 10 μM glibenclamide (K<sub>ATP</sub>), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (<i>p</i> < 0.05) reduced the ARI-induced relaxation. ARI significantly (<i>p</i> < 0.05) reduced the contractile response to agonist of Ca<sub>V</sub>1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.https://www.mdpi.com/1420-3049/24/15/2748Aristotelinevascular activitycalcium channelspotassium channelsrat |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fernando Romero Javier Palacios Ignacio Jofré Cristian Paz Chukwuemeka R. Nwokocha Adrián Paredes Fredi Cifuentes |
spellingShingle |
Fernando Romero Javier Palacios Ignacio Jofré Cristian Paz Chukwuemeka R. Nwokocha Adrián Paredes Fredi Cifuentes Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta Molecules Aristoteline vascular activity calcium channels potassium channels rat |
author_facet |
Fernando Romero Javier Palacios Ignacio Jofré Cristian Paz Chukwuemeka R. Nwokocha Adrián Paredes Fredi Cifuentes |
author_sort |
Fernando Romero |
title |
Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta |
title_short |
Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta |
title_full |
Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta |
title_fullStr |
Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta |
title_full_unstemmed |
Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta |
title_sort |
aristoteline, an indole-alkaloid, induces relaxation by activating potassium channels and blocking calcium channels in isolated rat aorta |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-07-01 |
description |
Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. <i>Aristotelia chilensis</i> (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl<sub>2</sub> (Kir), 10 μM glibenclamide (K<sub>ATP</sub>), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (<i>p</i> < 0.05) reduced the ARI-induced relaxation. ARI significantly (<i>p</i> < 0.05) reduced the contractile response to agonist of Ca<sub>V</sub>1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway. |
topic |
Aristoteline vascular activity calcium channels potassium channels rat |
url |
https://www.mdpi.com/1420-3049/24/15/2748 |
work_keys_str_mv |
AT fernandoromero aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT javierpalacios aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT ignaciojofre aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT cristianpaz aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT chukwuemekarnwokocha aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT adrianparedes aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta AT fredicifuentes aristotelineanindolealkaloidinducesrelaxationbyactivatingpotassiumchannelsandblockingcalciumchannelsinisolatedrataorta |
_version_ |
1725949211449491456 |