肾上腺髓质素2的降压作用及其机制

目的:研究肾上腺髓质素2(ADM2)拮抗血管紧张素Ⅱ(AngⅡ)发挥舒张血管的作用及机制。方法:将18只180~200 g雄性SD大鼠随机分为3组(n=6):对照组、AngⅡ(150 ng/(kg·min))组和AngⅡ(150 ng/(kg·min))+ADM2(500 ng/(kg·h))组,采用皮下埋植微量渗透泵的方法给药。2周后颈动脉插管法测量大鼠血压,测定血浆一氧化氮(NO)含量和内皮型一氧化氮合酶(eNOS)活性。DHE染色法检测大鼠动脉壁活性氧产生。制备大鼠离体血管环,观察ADM2的舒血管作用。培养人脐静脉内皮细胞系EA.hy 926,用DCFH-DA荧光探针检测AngⅡ和ADM2对血管内皮细胞活性氧释放的影响。结果:与AngⅡ组相比,ADM2显著降低了大鼠血压,血浆中eNOS活性提高、NO含量增加,血管壁活性氧产生减少。ADM2呈浓度依赖性和内皮依赖性舒张血管环,并明显抑制了AngⅡ引起的血管内皮细胞活性氧产生。结论:ADM2可能通过拮抗AngⅡ诱导的血管内皮氧化应激效应,改善内皮功能,发挥舒张血管、降低血压的作用。

The antihypertensive effect of adrenomedullin 2 and related mechanism

Objective： To observe the vasedilating effect of adrenomedullin 2 （ADM2） by antagonizing angiotensin Ⅱ（Ang Ⅱ）, and to explore its mechanism. Methods： Eighteen male, 180 - 200 g SD rats were randomly divided into 3 groups （ n = 6） ： control group, Angll （150 ng/（kg-min） ） group and AngⅡ （150 ng/（kg·min） ） ＋ ADM2（500 ng/（kg·h） ） group. Mini-osmotic pumps filled with peptide were implanted in the back of rats subcutaneously. After two weeks, the blood pressure was measured by the way of carotid inttrbatian. The plasma was collected for the detection of nitric oxide （NO） content and the activity of endothelial nitric oxide synthase （eNOS）. The in situ oxidation of fluorescent dye dihydroethidium （DHE） was used for detecting superoxide in rat arteries. The rat isolated arterial rings were made for studying the vasodilating effect of ADM2. Human umbilical vein endothelial cell hne EA. hy 926 cells were ctdtured and their intracellular reactive oxygen species （ROS） were evaluated by probe DCFH-DA. Results： ADM2 dramatically decreased the blood pressure in angiotensin Ⅱ-in- duced hypertension rat model, enhanced plasma NO content and the activity of eNOS and reduced superoxide formation in vessel walls. ADM2 also induced relaxation of the vascular rings preconstricted by Ang Ⅱ in a concentration-dependent and endothelium-dependent manner. In cultured vascular endothelium, ADM2 ameliorated the ROS generation induced by AngⅡ .Conclusion： Adrenomedttllin 2 relaxed blood vessels by antagonizing angiotensin Ⅱ-induced oxidative stress and improving the vascular endothelial function. KEY WORDS] hypertension; adrenomedullin 2; oxidative stress; endothelial dysfunction