Objective :To investigate the mechanism of reduced endothelium- dependent relaxation on cerebral basilar artery in spontaneously hypertensive rats (SHR). Methods:The mesenteric arteries of Wistar-Kyoto rats (WKY) were as control. The dilatory responses of vessels were assessed by cumulative addition of acetylcholine (ACh), pre-contracted with 20μM 5-hydroxytryptamine, to examine the change of endothelium-dependent relaxation in SHR. The effects of nitric oxide (NO)- , prostacyclin I2 (PGI2)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation were investigated in SHR artery one by one. The responses were characterized in terms of maximum relaxant effect (Rmax) and negative logarithm of the molar concentration that produced half maximum relaxation (pIC50). ANOVA Two-way and t test were used to analyze the data. Transmission electron microscopy was used to study the change of vascular mierostructure in SHR. Results :The Rmax and pIC50 were changed from 97％± 1 ％ and 8. 67± 0. 21 in WKY rats to 39％± 2％ (P＜O. 001) and 7. 05±0. 65 (P ＜ 0. 05), respectively in SHR. In NO-mediated relaxation, the Rmax and pIC50 were 53±2％ and 6. 89± 0. 33, respectively in WKY rats, and 32％±2％ (P＜O. 001) and 3. 93±0. 07 (P ＜0.001) , respectively in SHR. In PGI2-mediated relaxation , the Rmax and PIC50 were 8％± 1± and 4. 58± 0. 30, respectively in WKY rats, and 8％±1％ (P＞O. 05) and 4. 52±0. 27 (P＞0. 05), respectively in SHR. In EDHF-mediated relaxation, the Rmax and pIC50 were 35％± 5％ and 6. 30±0. 50, respectively in WKY rats,and 14％±1％(P＜0. 001) and 3. 85± 0. 07 (P ＜ 0. 001), respectively in SHR. Electron microscopy showed the microstructure of WKY rats cerebral basilar artery was normal, but SHR cerebral basilar artery appeared damaged , the endothelial cells had fallen off at some points, the endothelial layer showed no integrity,and the internal elastic membrane was not well-proportioned or ruptured. Conclusion:The reduced endothelium-dependent relaxation in SHR cerebral basilar artery may cause by The damage NO- and EDHF-mediated relaxation and damaged endothelium microstructures.%目的:探讨自发性高血压大鼠脑膜中动脉内皮依赖性舒张功能降低的机制.方法:以WKY为对照,观察 SHR大鼠脑膜中动脉环5-羟色胺预收缩后乙酰胆碱舒张性改变,考察一氧化氮途径,前列环素途径以及内皮源性超极化因子途径在SHR脑膜中动脉舒张功能的改变,反应特征表述为最大松弛百分率(Rmax)和产生一半最大松弛百分率时所需要ACh浓度的负对数(pIC50).ANOVA Two-way 和t检验分析组间差异.透射电镜法观察SHR脑膜中动脉内皮超微结构的改变.结果:WKY大鼠脑膜中动脉Rmax和pIC50 分别为97%±1%和8.67±0.21,SHR Rmax和pIC50分别为39%±2%(P<0.001)和7.05±0.65(P<0.05);NO途径在WKY 大鼠,Rmax和pIC50分别为53%±2%和6.89±0.33,在SHR Rmax和pIC50分别为32%±2%( P<0.001),和3.93±0.07(P <0.001);PGI2途径在WKY 大鼠,Rmax和pIC50分别为8%±1%和4.58±0.30,在SHR Rmax和pIC50分别为8%±1%,(P>0.05),和4.52±0.27,(P>0.05);EDHF途径在WKY 大鼠,Rmax和pIC50分别为35±5%和6.30±0.50,在SHR Rmax和pIC50分别为14%±1%,(P<0.001),和3.85±0.07,(P<0.001).电镜观察显示SHR脑膜中动脉出现部分内皮细胞脱落,内弹力膜不完整,有断裂现象.结论:NO-和EDHF-介导的舒张功能降低以及内皮超微结构受损参与导致SHR脑膜中动脉内皮依赖性舒张功能降低.
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