ABSTRACT
OBJECTIVE: French maritime pine bark extract (Flavangenol) has been known to produce an endothelium-dependent vasodilatory effect. In the present study, we evaluated whether a dietary supplementation of Flavangenol exhibits antihypertensive action using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Moreover, we investigated the mechanisms of an in-vitro vasorelaxant response to Flavangenol. METHODS AND RESULTS: The development of DOCA-salt-induced hypertension during a 5-week treatment period was significantly suppressed by feeding a Flavangenol-containing diet. Increased superoxide (O2-) production in vascular tissues after the DOCA-salt treatment tended to be suppressed by the Flavangenol feeding, whereas decreased vasorelaxant responses to acetylcholine in endothelium-intact aortas of DOCA-salt rats were significantly improved in Flavangenol-fed rats. Moreover, Flavangenol itself caused a potent endothelium-dependent vasorelaxation in aorta and mesenteric vascular bed. Pretreatment with a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, or a soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one abolished the Flavangenol-induced vasorelaxation in the aorta. At the same concentration, Flavangenol produced a rapid increase in phosphorylated-endothelial nitric oxide synthase (Ser1177) protein expression in aortic tissues, without affecting levels of total endothelial nitric oxide synthase protein expression. Flavangenol-induced vasorelaxant effect was not observed in aortic rings of endothelial nitric oxide synthase-deficient mice. Flavangenol feeding failed to suppress the development of hypertension in chronically nitric oxide synthase-inhibited rats. CONCLUSION: Thus, it seems likely that the antihypertensive effect of Flavangenol is attributable to both its antioxidative property-related protective effects against endothelial dysfunction and the endothelium-dependent vasorelaxant effect, which is mediated by endothelial nitric oxide synthase activation.
