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

Kwak, Chol-Juna; Kubo, Erikoa; Fujii, Kiwakoa; Nishimura, Yuria; Kobuchi, Shuheia; Ohkita, Mamorua; Yoshimura, Makikob; Kiso, Yoshinobub; Matsumura, Yasuoa

doi: 10.1097/HJH.0b013e3283186994
Original papers: Endothelium

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, 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 (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.

aLaboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan

bInstitute for Healthcare Science, Suntory Ltd., Mishima-gun, Osaka, Japan

Received 20 April, 2008

Revised 6 September, 2008

Accepted 8 September, 2008

Correspondence to Yasuo Matsumura, PhD, Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan Tel: +81 72 690 1051; fax: +81 72 690 1051; e-mail: matumrh@gly.oups.ac.jp

© 2009 Lippincott Williams & Wilkins, Inc.