Distilled Lupinus albus Seeds Induce Vasorelaxation by Activation of eNOS-NO-cGMP Pathway and Direct Inhibition of Voltage Dependent Calcium Channels

Abstract

Hypertension is a global health problem that needs exploration for new therapeutics. The community in North Western Ethiopia uses a local alcoholic beverage prepared from Lupinus albus L. seeds for the treatment of hypertension. Although this preparation has been traditionally used as an antihypertensive preparation, it lacks scientific evidence regarding efficacy and possible mechanisms of its antihypertensive action. The aim of this study was to investigate the ex vivo vasorelaxation activity and possible mechanisms of L. albus seed distillate (“gebto arekei”) in isolated guinea pig thoracic aorta. The vasorelaxation effect of different concentrations of the distillate (4 - 32 μg/ml) was investigated in isolated thoracic aorta strips pre-contracted by either epinephrine (1 μM) or potassium chloride (80 mM) using ex vivo isometric tension recording method. The extract induced vasorelaxation response in both endothelium intact and endothelium denuded strips as well as strips pre-incubated with NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB) in concentration-dependent manner. The distillate showed synergistic activity when combined with sodium nitroprusside. Determination of calcium concentration responses revealed significant inhibition of contraction. The concentration that caused maximal relaxation and 50% maximal relaxation was found to be 4.74 μg/ml and 3.80 μg/ml, respectively, in epinephrine pre-contracted endothelium intact strips, whereas it was 21 μg/ml and 7.01 μg/ml in strips pre-contracted with potassium chloride. Distilled L. albus seeds showed vasodilatory effect through endothelial nitric oxide synthase-nitric oxide-cyclic guanosine monophosphate pathway and direct inhibitory effect on voltage dependent calcium channels that supports its traditional use in the treatment of hypertension.