硫化氢对L-NAME诱导的高血压大鼠大脑微动脉肌源性反应的影响

Effect of hydrogen sulfide on the myogenic response of cerebral arterioles in L-NAME-induced hypertensive rats

目的探讨外源性硫化氢(H_(2)S)对N-硝基-L-精氨酸甲脂(L-NAME)诱导的高血压大鼠大脑微动脉肌源性反应的影响。方法健康雄性SD大鼠,随机分为正常对照组(Control组)、硫氢化钠(NaHS,H_(2)S供体)组、L-NAME组和NaHS+L-NAME组。14 d后,大鼠断头取脑,分离大鼠脑微动脉(直径150~200μm)进行离体加压灌流,记录微动脉在20~120 mmHg各压力点的血管直径。结果Control组大鼠脑血管直径在20 mmHg≤压力<40 mmHg压力范围时随压力升高而升高,在40~100 mmHg压力范围时随压力的升高逐渐降低,NaHS组大鼠脑微动脉肌源性反应和正常大鼠相同。与Control组相比,L-NAME诱导的高血压大鼠脑微动脉直径在40 mmHg压力条件下未见增加,而肌源性张力在40 mmHg和60 mmHg条件下明显增加。灌流液中加入NaHS可以使L-NAME诱导的高血压大鼠脑微动脉肌源性反应曲线上移,减弱了血管的肌源性张力;在NaHS+L-NAME组,NaHS连续注射后也可以使血管直径随压力的升高而缓慢增加,降低L-NAME对大鼠脑血管的肌源性张力的作用。结论H_(2)S可以降低L-NAME诱导的高血压大鼠脑微动脉肌源性反应和肌源性张力。

Objective To investigate the effect of hydrogen sulfide(H_(2)S)on the myogenic response of cerebral arterioles in N-nitro-L-arginine methylester(L-NAME)-induced hypertensive rats.Methods Male SD rats were randomly divided into four groups:a normal control(Control)group,a NaHS(H_(2)S donor)group,a L-NAME group and a NaHS+L-NAME group.After 14 days,the rats were decapitated and the brains were removed,and the cerebral arterioles(150-200μm in diameter)were isolated and cannulated for in vitro pressure perfusion.The diameters of the arterioles in response to increased perfusion pressure(from 20 to 120 mmHg,by 20 mmHg steps)were recorded.Results Rats in the Control group showed increases in cerebral arteriole diameter as the pressure was elevated from 20 to 40 mmHg,and decreases in cerebral arteriole diameter as the pressure was elevated from 40 to 100 mmHg.The myogenic response of cerebral arterioles in the NaHS group was similar to that in normal rats.Compared with the Control group,the cerebral arteriole diameter of L-NAME-induced hypertensive rats did not increase at 40 mmHg,while myogenic tone significantly increased at 40 and 60 mmHg.The addition of NaHS to the perfusate up-shift the myogenic response curve and reduced the myogenic tone of the cerebral arterioles in L-NAME-induced hypertensive rats.For the NaHS+L-NAME group,continuous injection of NaHS slowly elevated the arteriolar diameter which increased along with the rise in pressure,and reduced the effect of L-NAME on the myogenic tone of cerebral arterioles.Conclusions H_(2)S can reduce the myogenic response and myogenic tone of cerebral arterioles in L-NAME-induced hypertensive rats.