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

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree . 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 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 M) significantly reduced the contractile response to KCl ( < 0.001) more than PE ( < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10 M) drastically reduced the contraction to KCl (6·10 M), but after that, PE (10 M) caused contraction ( < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 × 10 M; < 0.01) and BaCl₂ (a non-selective inward rectifier potassium channel blocker; 5 × 10 M; < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10 M; < 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 Ca in a Ca free solution ( < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10 M; < 0.01), likely decreasing the influx of extracellular Ca through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine may be protective in the treatment of cardiovascular pathologies.