title: Vasodilation effect of 2-benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one.
abstract: A 2-Benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one (ZC2) is a newly synthesized isoquinolinone compound. Its effect on vasodilation was evaluated in the present study. Isometric tension of rat artery rings was recorded by a sensitive myography system in vitro. The results showed that ZC2 relaxed rat mesenteric arteries pre-contracted by KCl, phenylephrine and 9, 11- dideoxy- 11α, 9α-epoxymethano-prostaglandin F2α (U46619), and abdominal aorta pre-contracted by KCl in a concentration-dependent manner. The ZC2-induced vasodilation was not affected by an endothelium denudation. ZC2 rightwards shifted the concentration-contraction curves, induced by KCl, phenylephrine, and 5-hydroxytryptamine (5-HT) in a non-parallel manner, which suggests that the vasodilation effects are most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Moreover, in Ca(2+)-free medium, ZC2 concentration-dependently depressed the vasoconstrictions induced by phenylephrine and CaCl(2), and decreased a contractile response induced by caffeine, which indicates a role of extracellular Ca(2+) influx inhibition through VDCC and ROCC, and intracellular Ca(2+) release from Ca(2+) store via the ryanodine receptors. Glibenclamide did not affect the vasodilation induced by ZC2, suggesting that ATP sensitive potassium channel is not involved in the vasodilation. The results indicate that ZC2 induces vasodilation by inhibiting the VDCC and ROCC, and receptormediated Ca(2+) influx and release. The inhibition of intracellular Ca(2+) release may be mediated via the ryanodine receptors.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Xu
authors.forename: Zhi-Zheng
authors.initials: ZZ
authors.lastname: Xiong
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Chen
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Gao
authors.forename: Hang
authors.initials: H
authors.lastname: Yu
authors.forename: San-Qi
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C577454:2-benzyl-5-hydroxy-6-methoxy-3,4-dihydroisoquinolin-1-one; D044182:Benzylisoquinolines; D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002118:Calcium