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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。
Objective To investigate the effect of ranolazine on the tension of isolated renal artery in hybrids and its mechanism. Methods The body weight of hybrid dogs was 10-15 kg. After tracheal intubation anesthesia, heparin 500 IU / kg anticoagulant was administered rapidly and laparotomy. The kidneys were removed and placed in K-H solution with precooling oxygen at 4 ℃. The remaining blood was cleaned. An intrarenal artery was isolated by micromanipulation under an ice bath to prepare a 1.8-2.0 mm long vascular rod. Two stainless steel wires with a diameter of 40 μm were passed through the lumen of the vascular rod and fixed on the jaws in the microvascular vessel. Record changes in the tension of the blood vessels acting on the drug. Vasoconstrictor 1μmol·L-1, phenylephrine (Phe), 0.1μmol·L-1 thromboxane A2 receptor agonist (U46619) and 60 mmol·L-1 potassium chloride After contracting and stabilizing, ranolazine was added by cumulative administration method to observe the effect of different concentrations of ranolazine on canine renal artery tension induced by different contractile agents. Results Ranolazine showed a concentration-dependent relaxation of Phe precontracted endothelium, endothelium, or endothelial nitric oxide synthase (eNOS) inhibitor L-nitro-arginine methyl ester (Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME), the maximum values of P D2 were 6.32 ± 0.18, 6.35 ± 0.16 and 6.36 ± 0.04, respectively. The maximal relaxation rates were 97.78% ± 1.22%, 98.05% ± 3.24% and 94.71% ± 0.75% respectively. However, there was no obvious relaxation effect on U46619 and 60 mmol·L-1 potassium chloride precontracted renal artery rings. Conclusion Ranolazine has a concentration-dependent relaxation of Phe induced contraction of canine renal artery, and no significant endothelium-dependent.