ADMA损伤血管内皮后Apelin-13对大鼠血压的影响

The effect of apelin-13 on blood pressure in rats following vascular endothelial damage by asymmetric dimethylarginine

目的探讨在非对称性二甲基精氨酸(ADMA)导致大鼠血管内皮损伤的病理条件下,血管活性肽apelin-13对大鼠离体血管产生的效应及对血压的影响。方法成年雄性SD大鼠20只,分为ADMA组和对照组。用微量渗透泵给予两组大鼠分别持续注射ADMA[10 mg/(kg.d)]和生理盐水,28天。基线水平测量大鼠血压。28天后复测血压并检测血清ADMA、一氧化氮(NO)的浓度。给予大鼠尾静脉注射apelin-13(10 nmol/kg),观察血压变化。使用透射电镜观察大鼠尾动脉血管内皮细胞超微结构。行离体尾动脉实验观察apelin-13(10-10～10-5 mol/L)对两组血管环的作用。结果 28天后,ADMA组大鼠血清ADMA浓度明显高于对照组,而NO浓度降低。ADMA组大鼠收缩压较对照组明显升高(154±5 mmHg比123±4 mmHg,P<0.01)。静脉注射apelin-13(10 nmol/kg)后,ADMA组大鼠血压升至159±3 mmHg(P<0.05),而对照组降至113±3 mmHg(P<0.05)。透射电镜下可观察到ADMA组大鼠血管内皮细胞出现变性甚至坏死。离体血管实验表明apelin-13使ADMA组血管收缩而诱发对照组血管环舒张,呈浓度依赖性。结论 ADMA可对血管内皮细胞造成严重损伤,并导致大鼠高血压。在这种病理状态下,apelin-13可促进血管收缩,进而加重大鼠高血压。

Objectives Asymmetric dimethylarginine （ADMA） is a risk factor responsible to endothelial dysfunction, while the polypep- tide apelin is known to have biphasic effects on blood vessels. The effect of apelin - 13 on ADMA - damaged vessels in vivo and in vitro were stud- ied. Methods Twenty SD rats were divided into ADMA group and control group, and they were treated with subcutaneous infusions of ADMA （ 10 mg/kg/day） and saline, respectively, for4 weeks, by using osmotic mini - pumps. The plasma levels of ADMA and nitric oxide （NO） were examined. Systolic blood pressure （SBP） was measured before and after the injection of apelin - 13. The ultrastructural findings of endothelial cells in caudal arteries were examined by using transmission electron microscopy. In addition, the reactivities of isolated caudal artery rings in these two groups were observed after exposure to apelin - 13. Results Plasma levels of ADMA were elevated and NO concentrations were decreased in rats of ADMA group, and ADMA induced hypertension and endothelial dysfunction had been observed. After injection of apelin - 13, SBP de- clined in rats of control group but it was elevated in ADMA group. In vitro, apelin - 13 caused relaxation in rings in control group, but it contract- ed rings in ADMA group. Conclusion ADMA induces marked hypertension and impairments to endothelial cells in rats. Under the pathological condition, apelin - 13 can cause and exacerbate hypertension