Mechanism of hyperoside-induced dilatation in middle cerebral arteries of rats subjected to cerebral ischemia reperfusion / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the dilatation and mechanism of hyperoside (Hyp) in middle cerebral arteries (MCA) of rats subjected to cerebral ischemia reperfusion (CIR). METHODS: Rat isolated MCA segments were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate MCA vascular smooth muscle cell hyperpolarization. (1×10-6-1×10-4) mol·L-1 Hyp was used to investigate the effects on vasodilatation and hyperpolariza-tion in MCA of rats subjected to CIR. And the effects of nitric oxide synthase inhibitor (N-nitro-L-arginine-methyl-ester, L-NAME, 3×10-5 mol·L-1) or L-NAME plus prostaglandin I2 synthetase inhibitor (indomethacin, Indo, 1×10-5 mol·L-1) on vasorelaxation and hyperpolarization induced by Hyp were observed, respectively. Auto ELISA Detector and nitrate reductase methods were utilized to detect the H2 S and NO content in the cerebrum of rats. RESULTS: Hyp remarkably induced dose-dependent vasodilatation and hyperpolarization in 1×10-7 mol·L-1 U46619-preconstricted MCA of CIR rats. Hyp-mediated effects were notably attenuated after removal of endothelium in CIR MCA as compared with endothelium-intact group (P-5 mol·L-1) plus Indo (1×10-5 mol·L-1), the vasodilatation and hyperpolarization evoked by Hyp were significantly attenuated in sham operation group and CIR MCAs. Compared with the residual effects in sham vessels, those of CIR MCAs were remarkably potentiated (P-3 mol·L-1), an inhibitor of Ca2+-activated potassium channel, or PPG (1×10-4 mol·L-1), an inhibitor of the endogenous H2S synthese-CSE could markedly restrain Hyp-induced non-NO and non-PGP relaxation and hyperpolarization in sham and CIR vessels. As compared with CIR group, pretreatment with Hyp increased the H2S contents while decreased the NO contents. CONCLUSION: Hyp has the potential to evoke endothelium-dependent and endothelium-inde pendent effects in CIR MCAs. In these responses to Hyp, NO-mediated response is downregulated while endothelium-derived hyperpolarizing factor (EDHF) is upregulated, ie, endogenous H2S, is upregulated. Hyp can also protect the brain against cerebral ischemia injury by promoting H2S contents and decreasing NO contents of brain tissues.