内源性气态SO2对血管的舒张作用及其机制：细胞离子通道的作用

为了探讨内源性气态二氧化硫(SO2)对心血管功能的调节作用,首次采用SO2气体直接作用血管环的方法,观察SO2对血管环张力的影响及其与血管组织细胞离子通道的关系.结果发现:1)SO2气体不论在生理相关浓度范围内,还是在高浓度下均可剂量依赖性地引起血管环的舒张反应,EC50值为(1247.38±98.32)μmol·L-1.在生理浓度((110.34±35.22)μmol·L-1)和较低浓度下(<450μmol·L-1),SO2的舒张作用是内皮依赖性的,而在较高浓度下(>500μmol·L-1),SO2的舒张作用与内皮无关;2)硝苯地平(Nifedipine,L型钙通道阻断剂)可部分抑制较高浓度(1500μmol·L-1)SO2引起的舒张反应,而对较低浓度(30、300μmol·L-1)SO2引起的舒张反应无显著影响;3)四乙基氯化铵(TEA,非特异性钾通道阻断剂)则对较低浓度和较高浓度SO2引起的舒张反应均有部分抑制作用;4)格列本脲(Glibenclamide,ATP敏感的钾通道(KATP)的特异阻断剂)可部分抑制1500μmol·L-1SO2引起的舒张反应,而对30、300μmol·L-1SO2引起的舒张反应无显著影响;5)IbTx(Iberiotoxin,大电导钙激活钾通道(BKCa)阻断剂)只可部分抑制30、300μmol·L-1SO2引起的舒张反应,而对1500μmol·L-1SO2引起的舒张反应无显著影响.由此结论:内源性气态SO2对大鼠离体胸主动脉环有剂量依赖性的舒张作用;在生理浓度和较低浓度下,SO2的舒张作用是内皮依赖性的,其作用机制与BKCa通道有关;而在较高浓度下,SO2的舒张作用与内皮无关,其作用机制与KATP和L型钙通道等有关;气态SO2的生理作用远大于它的衍生物亚硫酸盐和亚硫酸氢盐.

The Vasorelaxant Effect of Endogenous Gaseous Sulfur Dioxide on Aortic Rings and Its Mechanism: Involvement of Ion Channels

To investigate the modulatory effect of endogenous gaseous sulfur dioxide(SO2)on the cardiovascular function, isolated rat aortic rings were directly treated by gaseous SO2 and observed the relation between the effect of SO2 and vascular cellular ion channels for the first time.Results showed that:1) gaseous SO2 could relax isolated aortic rings in a dose-dependent manner(EC50(:1247.38±98.32)μmol·L-1) at both physiological and high concentrations.The vasorelaxant effect of SO2 at physiological((110.34 ±35.22)μmol·L-1) and low concentrations(<450μmol·L-1) was endothelium-dependent, while it was endothelium-independent at high concentrations(>500μmol·L-1);2) the vasorelaxation of 1500μmol·L-1 SO2 on aortic rings was partially inhibited by nifedipine(the inhibitor of L-type calcium-channel), but the vasorelaxant effects of 30 and 300μmol·L-1 SO2 were not affected by nifedipine;3) vasorelaxation induced by SO2 at 30, 300 and 1500μmol·L-1 was partially inhibited by tetraethylammonium(TEA, the inhibitor of non-specific K+ channel);4) the vasorelaxant effects induced by 1500μmol·L-1 SO2 were partially inhibited by glibenclamide(the inhibitor of ATP-sensitive K(+KATP)channel), but the vasorelaxant effects of 30 and 300μmol·L-1 SO2 were not affected by glibenclamide;5) the vasorelaxant effects induced by 30 and 300μmol·L-1 SO2 were partially inhibited by iberiotoxin(IbTx, the inhibitor of big-conductance Ca2+-activated K+ channe(lBKCa)), but the vasorelaxant effects of 1500μmol·L-1 SO2 were not affected by IbTx.These results led to the conclusions that endogenous gaseous SO2 could cause significant vasorelaxation on rat aortic rings in a dose-dependent manner.The vasorelaxant effects of SO2 at physiological and low concentrations were endothelium-dependent, which might be partly related to BKCa channel.The mechanism of SO2-induced vasorelaxation at high concentrations was shown to be endothelium-independent, which might be related to KATP channel and L-type calcium-channel.Physiological effect of gaseous SO2 is stronger than that of its derivatives(Na2SO3, NaHSO3).