title: Sesamin metabolites induce an endothelial nitric oxide-dependent vasorelaxation through their antioxidative property-independent mechanisms: possible involvement of the metabolites in the antihypertensive effect of sesamin.
abstract: Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.
authors.affiliation: Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Chol-Jun
authors.initials: CJ
authors.lastname: Kwak
authors.forename: Kiwako
authors.initials: K
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikemura
authors.forename: Aiko
authors.initials: A
authors.lastname: Satake
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ono
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakai
authors.forename: Namino
authors.initials: N
authors.lastname: Tomimori
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kiso
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D004149:Dioxoles / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D004149:Dioxoles; D017705:Lignans; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C054125:sesamin