Protective effect and mechanism of total flavones from Rhododendron simsii Planch on endothelium-dependent dilatation and hyperpolarization in cerebral ischemia-reperfusion and correlation to hydrogen sulphide release in rats

Abstract

We for the first time investigated the effect and mechanism of the total flavones of Rhododendron simsii Planch (TFR), a widely-used Chinese herb for a thousand years, on vasodilatation and hyperpolarization in middle cerebral artery (MCA) of rats subject to global cerebral ischemia-reperfusion (CIR). TFR (112700 mg/L) evoked dose-dependent vasodilation and hyperpolarization in MCA of both sham and CIR that were partially inhibited by 30 M N-nitro-L-arginine- methyl-ester and 10 M indomethacin and further attenuated by endogenous H 2S synthese-CSE inhibitor PPG (100 M) or Ca2+-activated potassium channel (K ca) inhibitor TEA (1 mM). In whole-cell patch clamp recording, TFR remarkably enhanced the outward current that was inhibited by TEA. CIR increased CSE mRNA expression and the contents of H2S that were further increased by TFR. We conclude that, in MCA of CIR rats, TFR induces non-NO and non-PGI2-mediated effects of vasodilatation and hyperpolarization involving K ca and increases CSE mRNA expression level in endothelial cells and H2S content in the cerebrum. These findings suggest that the response induced by TFR is potentially related to endothelium-derived hyperpolarizing factor mediated by the endogenous H 2S and promote the use of TFR in protection of brain from ischemia-reperfusion injury. © 2014 Jun Han et al.