辛二酰苯胺异羟肟酸舒张大鼠离体胸主动脉作用和机制

目的研究辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)对大鼠离体胸主动脉环的作用和舒张机制。方法采用离体大鼠胸主动脉环灌流,观察累积浓度SAHA(0.3、1、3、10和30μmol·L^-1)对基础状态、KCl和NE预收缩的大鼠离体胸主动脉环的作用,同时使用工具药L-NAME、Indo、PMA和SP来研究其舒张血管的可能机制,并探讨SAHA在舒张血管过程中对Ca²⁺的作用。结果SAHA能够舒张KCl和NE预收缩的大鼠离体胸主动脉(P<0.01),且对完整内皮胸主动脉作用强于去内皮胸主动脉(P<0.01),但对基础状态无明显影响;L-NAME、Indo和PMA可抑制SAHA的血管舒张作用(P<0.05),而SP能够促进其舒张血管(P<0.01);SAHA可抑制外钙内流和内钙释放而减弱CaCl 2和NE诱导的血管收缩作用(P<0.01)。结论SAHA舒张血管可能与增加内皮舒张因子NO和PGI 2生成,抑制PKC及外钙内流和内钙释放有关。

Vasodilating effect of suberoylanilide hydroxamic acid on isolated thoracic aorta of rats and its mechanisms

Aim To investigate the vasodilating effect of suberoylanilide hydroxamic acid(SAHA)on isolated thoracic aorta of rats and the possible mechanisms.Methods Isolated thoracic aorta of rats were used to perfuse,and to observe the effect of accumulated concentration of SAHA(0.3,1,3,10 and 30μmol·L^-1)on isolated thoracic aorta at basal state,KCl and NE precontracted state.At the same time,L-NAME,Indo,PMA and SP were used to explore its possible mechanisms of relaxing isolated thoracic aorta,and to investigate the role of the Ca²⁺during the vasodilating process.Results SAHA could relax KCl and NE precontracted isolated thoracic aorta of rats(P<0.01),and the effect on endothelium-intact was stronger than that on endothelium-denuded thoracic aorta(P<0.01),but there was no significant effect on thoracic aorta at basal state.The vasodilatory effect of SAHA could be inhibited by L-NAME,Indo and PMA(P<0.05),while that could be promoted by SP(P<0.01).SAHA could attenuate vasoconstriction induced by CaCl 2 and NE through inhibiting extracellular Ca²⁺influxe and intracellular Ca²⁺release in a concentration-dependent manner(P<0.01).Conclusions The vasodilating mechanisms of SAHA may be related to the increased production of vasodilatory factors NO and PGI 2,and the inhibition of PKC,and the inhibition of extracellular Ca²⁺influxe and intracellular Ca²⁺release.