OBJECTIVE: To investigate the improvement effect of atorvastatin on endothelial dysfunction of mesenteric arteries in spontaneously hypertensive rats (SHRs). METHODS: Wistar-Kyoto (WKY) rats were included as control group (normal saline), and other SHRs were divided into model group (normal saline) and atorvastatin group (10 mg-kg-1d-1) with 8 rats in each group. Those rats were given relevant medicine intragastrically for 8 weeks then sacrificed. Sensitive muscular tension graphic record was used to determine the effect of isolated mesenteric arterial ring tension on relaxing and contractile response induced by KC1, phenylephrine (PE) and Ach and the effect of ascorbic acid (100 μmol-L-1) and NOS inhibitor L-NAME (100 μmol-L-1) on Ach relaxing response. RESULTS: Compared with control group, the contractile responses to KC1 and PE were increased significantly in model group (P<0.01). Ach-induced relaxation was significantly impaired (P<0.01). Treatment with atorvastatin decreased the exaggerated vasocontractile responses and increased relaxation to Ach. Relaxation to Ach was inhibited by L-NAME in control group and there was no change in model group. Atorvastatin restored the inhibitory effect of L-NAME on Ach-induced relaxation. Ascorbic acid promoted Ach-induced relaxation in model group while played no effect in control group. Ascorbic acid no longer exerted its facilitating effect after atorvastatin treatment. CONCLUSION: Atorvastatin ameliorates endothelial dysfunction mesenteric arteries in SHRs by increasing antioxidant activity and/or the availability of NO.%目的:研究阿托伐他汀对自发性高血压大鼠(SHRs)肠系膜动脉内皮功能障碍的改善作用.方法:取京都种维斯特大鼠(WKYs)为对照组(生理盐水),另取SHRs分为模型组(生理盐水)和阿托伐他汀组(10 mg·kg-1·d-1),每组8只,灌胃给予相应药物,连续8周,处死后采用敏感的肌张力描记技术测定各组大鼠离体肠系膜动脉环对KC1、苯肾上腺素(PE)、乙酰胆碱(Ach)引起的收缩/舒张反应的张力变化,以及抗坏血酸( 100 μmol·L-1)和一氧化氮合酶(NOS)拮抗药N-硝基-L-精氨酸甲酯(L-NAME)(1 00μmol- L-)对Ach舒张反应的影响.结果:与对照组比较,模型组大鼠动脉环对KC1和PE引起的最大收缩反应明显增强(p＜0.01),对Ach的最大舒张反应明显减弱(P＜0.01)；而阿托伐他汀组可对抗模型组的上述作用.L-NAME可抑制对照组Ach的舒张反应,但不能影响模型组,阿托伐他汀治疗后恢复了L-NAME对Ach舒张反应的抑制作用.抗坏血酸可促进模型组Ach的舒张反应,但不能影响对照组,阿托伐他汀作用后抗坏血酸的作用消失.结论:阿托伐他汀可以通过提高抗氧化能力和/或增加NO的利用度采改善自发性高血压大鼠肠系膜动脉的内皮功能障碍.
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