奥美沙坦改善内皮素诱导的大鼠高血压与氧化应激

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂奥美沙坦对内皮素-1(ET-1)诱导的高血压大鼠氧化应激的影响。方法 5～6周雄性SD大鼠随机分为4组:①对照组(1%氯化钠慢性灌注,n=7);②ET-1慢性灌注组[2.5 pmol/(g.min),n=7];③ET-1+奥美沙坦治疗组(0.01%食物中混入,n=7);④ET-1+非特异性抗高血压药肼苯哒嗪治疗组[15 mg/(kg.d)饮水中给入,n=6]。测量大鼠第0、7、14天时的尾动脉收缩压。放射免疫法检测血浆肾素活性(PRA)和AngⅡ水平。免疫印迹法检测血浆血管紧张素原(AGT)水平和主动脉AT1受体表达。光泽精化学发光体系测定主动脉超氧化物阴离子产物(O2-)。结果与对照组相比,ET-1慢性灌注组大鼠血压明显升高[(121±2)vs.(141±2)mmHg,P<0.05],PRA明显增加[(3.1±0.6)vs.(8.1±0.8)AngⅠ/(mL.h),P<0.05)],AngⅡ水平明显升高[(47±7)vs.(94±13)fmol/mL,P<0.05];O2-[(16±1)vs.(27±1)CPM/mg]、血浆TBARS水平[(5.1±0.1)vs.(8.9±0.8)μmol/L]显著升高(P<0.05)。结论 ET-1、AngⅡ以及氧化应激的共同作用,促进了ET-1慢性灌注大鼠高血压的发展。奥美沙坦能改善ET-1诱导的大鼠高血压和氧化应激。

Improvement of olmesartan on hypertension and oxidative stress induced by endothefine-1 in rats

Objective To determine the effects of AT1 receptor blockade on reactive oxygen species(ROS)formation in ET-1-dependent hypertension.Methods Male SD rats were randomly treated with one of the following combinations for 2 weeks:①control group:Chronic 1 % NaCl infusion(n=7);②Chronic ET-1 infusion[2.5 pmol/(kg·min),n=7];③ET-1+Olmesartan(0.01% in chow,n=7);④ET-1+hydralazine[15 mg/(kg·d)]in drinking water(n=6).Results Chronic ET-1 infusion into rats increased systolic blood pressure.ET-1-infused rats showed greater plasma renin activity[(8.1±0.8)AngⅠ/(mL·h)]and AngⅡ levels[(94±13)fmol/mL]than those of 0.9 % NaCl-infused rats[(3.1±0.6)AngⅠ/(mL·h),and(47±7)fmol/mL,respectively,P<0.05].Vascular superoxide anion(O-2)production and plasma thiobarbituric acid-reactive substance(TBARS)levels were greater in ET-1-infused rats[(27±1)CPM/mg dry tissue weight and(8.9±0.8)mol/L,respectively)than those of 0.9 % NaCl-infused rats[(16±1)CPM/mg and(5.1±0.1)mol/L,respectively,P<0.05].Conclusion The combined effects of the elevations in circulating ET-1 and AngⅡ,as well as the associated oxidative stress,may contribute to the development of hypertension induced by chronic ET-1 infusion.Olmesartan can improve the hypertension and oxidative stress induced by endotheline-1 in rats.