title: Hesperetin inhibits rat coronary constriction by inhibiting Ca(2+) influx and enhancing voltage-gated K(+) channel currents of the myocytes.
abstract: Hesperetin (HSP, one of the most common flavonoids in Citrus) has been reported to possess many benificial effects and is indicated for many diseases both as a therapeutic drug and as a supplement. Although its vascular effects have been extensively studied, little is known about its effects and the underlying mechanisms on coronary artery. In the present study, the myogenic effects of HSP were studied with a wire myograph in isolated rat coronary artery (RCA). Molecular probe and the patch clamp technique were used to study effects of HSP on intracellular free Ca(2+) concentration, inward Ca(2+) currents through L-type voltage-gated Ca(2+) channels (LVGC) and outward K(+) currents through voltage-gated K(+) channels (KV). HSP (0.01-0.1mM) concentration-dependently depressed concentration-contraction curves of both KCl and thromboxane receptor agonist 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619), and relaxed RCA precontracted by the both vasoconstrictors. The vasospasmolytic effect was more potent in KCl- than in U46619-induced contraction. The vasorelaxation was attenuated by 4-aminopyridine, a specific KV inhibitor, but not affected by NG-nitro-L-arginine methylester ester, indomethacin, glibenclamide, iberiotoxin, BaCl2 or endothelium denudation. At the same concentrations, HSP inhibited extracellular Ca(2+) influx-induced contraction, reduced intracellular free Ca(2+) concentration, inhibited inward Ca(2+) currents through LVGC and increased outward K(+) currents through KV in the vascular smooth muscle cells (VSMCs) freshly isolated from RCA. Collectively, our results show that HSP is vasospasmolytic in RCA and suggest that the vasospasmolysis is mediated by inhibition of LVGC and enhancement of KV currents in RCA VSMCs.
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Longgang
authors.initials: L
authors.lastname: Niu
authors.affiliation: Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China.
authors.forename: Xuanping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China; Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Shanxi Province, Taiyuan 030001, China. Electronic address: zmspharmacol@sina.com.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006569:Hesperidin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D024642:Potassium Channels, Voltage-Gated; D006569:Hesperidin; C013015:hesperetin; D002118:Calcium
keywords: 4-aminopyridine: PubChem CID 1727; 9,11-Dideoxy-9a,11a- methanoepoxy prostaglandin F(2α) (U46619): PubChem CID 5311493; Coronary artery; Hesperetin; Hesperetin: PubChem CID 72281; Iberiotoxin: PubChem CID 24895960; Indomethacin: PubChem CID 3715; L-type voltage-gated calcium channels; NG-nitro-L-arginine methylester ester: PubChem CID 26759250; Nifedipine: PubChem CID 4485; S-(−)-1,4-Dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (Bay K 8644): PubChem CID 2303; Vasorelaxation; Voltage-gated potassium channels