title: Cellular mechanisms underlying Hyperin-induced relaxation of rat basilar artery.
abstract: OBJECTIVE
  Hyperin, a flavonol compound extracted from the Chinese herb Abelmoschus manihot L. Medic, is reported to exert protective actions in cerebral ischemic injury. The specific aim of the present study was to study the relaxation of Hyperin in rat isolated basilar artery and identify the underlying cellular mechanisms.
  
  
  METHODS
  Rat isolated basilar artery segments were cannulated and perfused while being superfused with PSS solution. Vessel images were recorded by video microscopy and diameters measured. Membrane potential was recorded using glass microelectrodes to evaluate the basilar artery smooth muscle cell hyperpolarization.
  
  
  RESULTS
  Perfusion of Hyperin (1~100 μM) elicited a concentration-dependent relaxation of basilar artery segments preconstricted with 0.1 μM U46619. The response was significantly inhibited by the removal of the endothelium. Hyperin also elicited marked and concentration-dependent hyperpolarization of smooth muscle cells. 30 μM nitro-L-arginine (an inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of cyclooxygenase), partially inhibited Hyperin-induced relaxation and hyperpolarization leaving an attenuated, but significant, endothelium-dependent relaxation and hyperpolarization. This remaining effect was almost completely blocked by 1mM tetraethylammonium (an inhibitor of Ca(2+)-activated K(+) channels), or by 100 μM DL-propargylglycine, an inhibitor of cystathionine-γ-lyase (a synthase of the endogenous H(2)S).
  
  
  CONCLUSIONS
  These findings show that Hyperin produces significant hyperpolarization in rat basilar artery smooth muscle cells and relaxation through both endothelium-dependent and endothelium-independent mechanisms. The underlying mechanisms appeared to be multi-factorial involving nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Our data further suggest that endogenous H(2)S is a component of the EDHF-mediated hyperpolarization and relaxation to Hyperin.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Fan
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Song
mesh_terms: D000480:Alkynes; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007213:Indomethacin; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D019335:Nitroarginine; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000480:Alkynes; D004365:Drugs, Chinese Herbal; D019335:Nitroarginine; C009055:propargylglycine; D019789:Tetraethylammonium; C021304:hyperoside; D011794:Quercetin; D005998:Glycine; D007213:Indomethacin; D006862:Hydrogen Sulfide