Vasodilatory Effects of Aqueous Extract from Harungana madagascariensis Stem Bark in Isolated Rat Aorta: The Roles of Endothelium and K+ Channels

Background: Hypertension is the most modifiable risk factor for cardiovascular diseases worlwide. It is one of the leading causes for mortality, as it may be asymptomatic but a lot of complications will develop rapidly and leading to death. Prevention and control of hypertension decreases mortality, and heart failure. The aim of this study was to investigate the vascular activity of aqueous extract obtained from stem bark of Harungana madagascariensis (Hypericaceae) and to determine the pharmacological mechanisms of the extract on rat aorta in vitro. Methods and Findings: The activity of different concentrations of H. madagascariensis aqueous extract (HMAE) was evaluated on contractile responses of isolated aorta to phenylephrine (PE, 1 μM) and potassium chloride (KCl, 60 mM). Then, various pharmacological agents were used to assess the involved vascular mechanisms. The extract (10-3- 8.10-1 mg/mL and 6.10-1-1 mg/mL) induced a concentration dependent relaxation respectively in aortic rings precontracted by PE and KCl. The effect on PE-preconstricted aortic rings was significantly reduced after endothelium removal, whereas it was enhanced on KCl-preconstricted rings. L-NAME, methylene blue and indomethacin as well as tetraethylammonium and barium chloride reduced significantly this vasorelaxation after PE-induced contraction. The vasorelaxant effect of sodium nitroprusside was not modified in the presence of HMAE. Conclusions: The involvement of NO-cGMP as well as prostacyclin-cAMP pathways contributes to the endothelium-dependent relaxant effects of HMAE after PEinduced contraction. Contribution of Ca2+-activated K+ channels, voltage-activated K+ channels and K+ inward rectifier channels as endothelium-independent mechanisms could also explain its vasorelaxants effects. The observed data suggest that HMAE has potential effects as phytoalternative treatment for hypertension and other cardiovascular diseases.