中文摘要：

目的观察雷诺嗪（ranolazine）对杂种犬离体肾内动脉张力的影响及其机制。方法杂种犬体质量10~15 kg,气管插管麻醉后,肝素500 IU/kg抗凝,迅速开腹,取下肾脏,置于4℃预冷氧饱和的K-H液中,清洗干净残留血液。冰浴下显微操作分离出肾内动脉,制备成1.8~2.0 mm长的血管条,用两根直径40μm的不锈钢丝穿过血管条管腔,固定在微血管测定仪浴槽内的钳夹上,记录血管对药物作用产生的张力变化。分别给予血管收缩剂1μmol·L-1苯肾上腺素（phenylephrine,Phe）、0.1μmol·L-1血栓素A2受体激动剂（U46619）和60 mmol·L-1氯化钾刺激血管产生持续性收缩,平稳后,采用累积给药法加入雷诺嗪,观察不同浓度的雷诺嗪对不同收缩剂诱导犬肾内动脉张力的影响。结果雷诺嗪分别呈浓度依赖性舒张Phe预收缩内皮完整的、去内皮的或用内皮一氧化氮合酶（endothelial nitric oxide synthase,e NOS）抑制剂L-硝基-精氨酸甲酯（Nω-nitro-L-arginine methyl ester hydrochloride,L-NAME）孵育的肾内动脉环,其p D2分别为6.32±0.18、6.35±0.16、6.36±0.04,其最大舒张率（Emax）分别为97.78%±1.22%,98.05%±3.24%和94.71%±0.75%;但对U46619和60 mmol·L-1氯化钾预收缩的肾动脉环无明显舒张作用。结论雷诺嗪有呈浓度依赖性舒张Phe诱导犬肾内动脉收缩的作用,且无明显内皮依赖性。

英文摘要：

Objectives To determine the effect and mechanism of ranolazine on mongrel dog intrarenal arteries in vitro.Methods Mongrel dogs weighing 10-15 kg were anaesthetized by intratracheal intubation, injected with 500 IU / kg of heparin to anticoagulation. After opening abdomen, the kidneys were removed quickly and placed in precooled（4℃） of oxygen-saturated K-H solution. Residual blood was washed out. The intrarenal arteries were dissected from kidneys under microscope and cut into two ring segments（1.8-2.0 mm in length）. Each segment was inserted with two tungsten wires（each 40 μm in diameter） through the segment lumen and mounted in a Multi Myograph System. Changes in arterial tone were recorded. 1 μmol·L-1of phenylephrine（Phe）, 0.1 μmol·L-1of thromboxane A2 receptor agonist,11-dideoxy-11 a, 9a-epoxy-methanoprostaglandin F2a（U46619） and 60 mmol·L-1of KCl were used individually to produce sustained contractions in renal arteries, then ranolazine was applied cumulatively. Results Ranolazine induced concentration-dependent relaxations in endothelium-intact rings, endothelium-denuded rings or endothelial nitric oxide synthase（e NOS） inhibitor Nω-nitro-L-arginine methyl ester hydrochloride（L-NAME） pre-incubated rings contracted with Phe, p D2 were 6.32 ±0.18, 6.35 ±0.16 and 6.36 ±0.04 respectively; Emax was 97.78% ±1.22%,98.05% ±3.24% and 94.71% ±0.75% respectively; but it failed to relax the rings contracted with U46619 or KCl.Conclusions Ranolazine has a concentration-dependent relaxant effect on mongrel dog intrarenal arteries, which is endothelium-independent.