Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta

• Main Authors: Fernando Romero, Javier Palacios, Ignacio Jofré, Cristian Paz, Chukwuemeka R. Nwokocha, Adrián Paredes, Fredi Cifuentes
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Molecules
• Subjects: Aristoteline; vascular activity; calcium channels; potassium channels; rat
• Online Access: https://www.mdpi.com/1420-3049/24/15/2748

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 &#956;M). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 &#956;M) 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 &lt; 0.05) decreased. Interestingly, the potassium channel blockade with 10 &#956;M BaCl₂ (Kir), 10 &#956;M glibenclamide (K_ATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (<i>p</i> &lt; 0.05) reduced the ARI-induced relaxation. ARI significantly (<i>p</i> &lt; 0.05) reduced the contractile response to agonist of Ca_V1.2 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.