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


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.


CONCLUSIONS
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.
Kwak
Chol-Jun
CJ
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Kubo
Eriko
E
Fujii
Kiwako
K
Nishimura
Yuri
Y
Kobuchi
Shuhei
S
Ohkita
Mamoru
M
Yoshimura
Makiko
M
Kiso
Yoshinobu
Y
Matsumura
Yasuo
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003900:Desoxycorticosterone; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D044946:Biflavonoids; D010936:Plant Extracts; D044945:Proanthocyanidins; C504746:flavangenol; D013481:Superoxides; D019335:Nitroarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D052250:Nitric Oxide Synthase Type III