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 (11~2700 mg/L) evoked dose-dependent vasodilation and hyperpolarization in MCA of both
sham and CIR that were partially inhibited by 30 μM N-nitro-
L-arginine-methyl-ester and 10 μM
indomethacin and further attenuated by endogenous H2S synthese-CSE inhibitor PPG (100 μM) or Ca(2+)-activated
potassium channel (Kca) 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 Kca 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 H2S and promote the use of TFR in protection of brain from
ischemia-reperfusion injury.