Antihypertensive effect of French maritime pine bark extract (Flavangenol): possible involvement of endothelial nitric oxide-dependent vasorelaxation

作者：Kwak Chol Jun; Kubo Eriko; Fujii Kiwako; Nishimura Yuri; Kobuchi Shuhei; Ohkita Mamoru; Yoshimura Makiko; Kiso Yoshinobu; Matsumura Yasuo^*

来源：Journal of Hypertension, 2009, 27(1): 92-101.

DOI：10.1097/HJH.0b013e3283186994

• antihypertensive effects
• antioxidative
• nitric oxide
• pine bark extract

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 (O(2)(-)) 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, N(G)-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 (Ser(1177)) 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.

• 出版日期2009-1