title: Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.
abstract: Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan. kamata@hoishi.ac.jp
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
authors.forename: Ayako
authors.initials: A
authors.lastname: Makino
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kanie
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Oda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Honda
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D020110:Pinacidil / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D001786:Blood Glucose; D014665:Vasodilator Agents; D020110:Pinacidil; D000109:Acetylcholine; D005905:Glyburide