内源性气态SO_2对血管的舒张作用及其机制Ⅲ：信号转导途径

The Vasorelaxant Effect of Endogenous Gaseous Sulfur Dioxide on Aortic Rings and Its Mechanism:Signal Transduction Pathways

为了从信号转导途径的角度探讨内源性气态SO2引起血管舒张的机制,采用将气态SO2或SO2生理盐水溶液加入孵育液的方法,使SO2分子直接作用于离体大鼠胸主动脉血管环,同时使用不同信号转导途径抑制剂,研究了内源性气态SO2诱发血管舒张的信号转导机制,并采用类比法研究了SO2对Krebs液pH的影响及其与血管舒张的关系.结果显示:1)内源性气态SO2对大鼠血管的舒张作用是SO2分子直接作用引起的,与SO2引起的pH值轻度降低无关;2)气态SO2在生理浓度和低浓度(<450μmol·L-1)引起的舒血管作用主要是通过NO/cGMP途径介导;3)很低浓度的气态SO(23μmol·L-1)和NO(3或5nmol·L-1)在引起血管舒张作用时有协同作用,二者在体内联合发挥对血管张力的调节作用.结论:1)SO2是血管组织的一种内源性气体舒张因子;2)SO2与NO可以协同调节血管张力,二者可能存在某种形式的交叉对话作用.

To explore cell signal transduction pathways by which vasorelaxant effect caused by endogenous gaseous sulfur dioxide（SO2）, isolated rat thoracic aortic rings were exposed directly to SO2 gas or SO2 gas-bubbled saline, and effects of inhibitors of different signal transduction pathways on vasorelaxation by gaseous SO2 on the rings were investigated. At one time relationship between effects of vasorelaxation and pH decrease of Krebs solution caused by SO2 was studied using anology method. Results showed that 1）The vasodilator effect induced by SO2 gas at the concentrations tested was actually caused by SO2 molecules, not by slight decrease of pH value, which was caused by adding of SO2 gas or the gas-bubbled solution into Krebs buffer. 2）The vasorelaxant effect of SO2 at the physiological relevant and low （〈450μmol·L^-1） concentrations was mediated by the NO/cGMP pathway. 3）There was the synergistic effect on smooth muscle relaxation between much lower concentrations of SO2 （3μmol·L^-1 ） and NO （ 3 or 5nmol·L^-1 ）. These results led to the conclusions： 1 ）SO2 was an endogenous gaseous vasoactive factor; 2）SO2 might regulate vascular smooth muscle tone in synergy with NO, suggesting there was some forms of ＂cross-talks＂ between SO2 and NO in vascular tissue.