摘要
目的探讨血管紧张素转换酶2(ACE2)特异性激动剂乙酰甘氨酸重氮氨苯脒(DIZE)对醋酸去氧皮质酮(DOCA)-盐敏感性高血压大鼠血压及血压变异性(BPV)的影响。方法36只雄性Sprague-Dawley(SD)大鼠随机分为Sham组(n=10),DOCA组[n=13,DOCA 50 mg/(kg·周),皮下注射2次/周],DIZE组[n=13,DOCA 50 mg/(kg·周),皮下注射2次/周+DIZE 15 mg/(kg·d),皮下注射1次/d]。采用Softron BP-98A无创血压仪测大鼠尾动脉血压,1次/周,共8周。以血压标准差、变异系数作为BPV的指标,分别计算短时BPV(重复测量3次之间的BPV)和长时BPV(0~1、0~2、0~3、0~4、0~5、0~6、0~7、0~8周的BPV)。酶联免疫吸附试验(ELISA)法测定各组大鼠血浆中血管紧张素(1-7)[Ang(1-7)]含量。结果与Sham组比较,DOCA组大鼠尾动脉收缩压、舒张压、平均动脉压均在实验第1周时升高,脉压于第3周一过性增高、于第5周再升高,持续至实验第8周(均P<0.05)。与Sham组比较,DOCA组大鼠长时收缩压变异性从第1周时开始增高[0~1周标准差:(7.26±3.14)比(3.81±2.37)mm Hg,变异系数:(6.21±2.74)%比(3.50±2.23)%,P<0.05],长时舒张压变异性于第4周开始增高[0~4周标准差:(19.44±7.05)比(10.66±2.59)mm Hg,变异系数:(18.72±6.06)%比(12.70±4.03)%,P<0.05],长时平均动脉压变异性从第2周时增高[0~2周标准差:(11.59±4.85)比(7.44±2.57)mm Hg,P<0.05],长时脉压变异性从第5周时升高[0~5周标准差:(11.41±2.29)比(9.25±1.88)mm Hg,P<0.05],持续至第8周。与DOCA组比较,DIZE组大鼠尾动脉收缩压于第2周降低,舒张压与平均动脉压在第4周时降低(P<0.05),长时收缩压变异性于第2周时降低,长时平均动脉压变异性于第4周时降低(均P<0.05),持续至第8周。各组大鼠短时BPV差异无统计学意义(P>0.05)。与Sham组相比,DOCA组大鼠血浆Ang(1-7)含量降低[(25.10±18.52)比(59.14±18.51)ng/L,P<0.05],与DOCA组相比,DIZE组大鼠血浆Ang(1-7)含量增加[(42.61±13.70)比(25.10±18.52)ng/L,P<0.05]。结论ACE2激动剂DIZE降低DOCA-盐敏感性高血压大鼠血压、长时收缩压变异性、长时平均动脉压变异性,且对收缩压及长时收缩压变异性的影响更早,这可能与ACE2激活、血浆Ang(1-7)水平升高有关。
Objective To investigate the effect of diminazene aceturate(DIZE),an angiotensin converting enzyme 2(ACE2)agonist,on blood pressure and blood pressure variability(BPV)in deoxycorticosterone(DOCA)-salt sensitive hypertensive rats.Methods Male Sprague-Dawley(SD)rats(n=36)were randomly divided into Sham group(n=10),DOCA group[n=13,DOCA 50 mg/(kg·week)]and DIZE group[n=13,DOCA 50 mg/(kg·week)+DIZE 15 mg/(kg·d)].The tail artery blood pressure was measured by Softron BP-98 A pressure meter weekly for 8 weeks.Standard deviation(SD),coefficient of variation(CV)were used as indicators of BPV.Short-term BPV(BPV among 3 repeated measurements)and long-term BPV(BPV of 0-1,0-2,0-3,0-4,0-5,0-6,0-7,0-8 weeks)were calculated respectively.The angiotensin(1-7)[Ang(1-7)]content in rat plasma was determined by enzyme-linked immunosorbent assay(ELISA)in three groups.Results Compared with the Sham group,the systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MAP)in the DOCA group increased at the first week of the experiment(P<0.05),and the pulse pressure transiently increased in the third week and then increased again at the fifth week until the eighth week(P<0.05).Compared to Sham group,in DOCA group long-term systolic blood pressure variability(SBPV)increased from 1 week[during 0-1 week,SD:(7.26±3.14)vs(3.81±2.37)mm Hg,CV:(6.21±2.74)%vs(3.50±2.23)%,P<0.05],long-term diastolic blood pressure variability(DBPV)from 4 weeks[during 0-4 week,SD:(19.44±7.05)vs(10.66±2.59)mm Hg,CV:(18.72±6.06)%vs(12.70±4.03)%,P<0.05],long-term mean arterial pressure variability(MAPV)from 2 weeks[during 0-2 week,SD:(11.59±4.85)vs(7.44±2.57)mm Hg,P<0.05],long-term pulse pressure variability from 5 weeks[during 0-5 week,SD:(11.41±2.29)vs(9.25±1.88)mm Hg,P<0.05]respectively.Compared with the DOCA group,in the DIZE group the SBP decreased at the second week,DBP and MAP decreased at the fourth week(P<0.05),the long-term SBPV decreased from 2 weeks,long-term MAPV decreased from 4 weeks(all P<0.05)respectively.There was no significant difference in short-term BPV among the three groups(P>0.05).Compared with the Sham group,the plasma Ang(1-7)content in the DOCA group decreased[(25.10±18.52)vs(59.14±18.51)ng/L,P<0.05],but increased in the DIZE group compared with the DOCA group[(42.61±13.70)vs(25.10±18.52)ng/L,P<0.05].Conclusion ACE2 agonist DIZE could reduce the blood pressure,long-term SBPV and MAPV in DOCA-salt sensitive hypertensive rats,and the effects of DIZE on SBP and long-term SBPV happens at early stage.This phenomenon may be related to ACE2 activation and then elevated plasma Ang(1-7)levels.
作者
左康家
商黔惠
刘婵
刘娟
赵宇
ZUO Kang-jia;SHANG Qian-hui;LIU Chan;LIU Juan;ZHAO Yu(Institute of Clinical Medicine,Institute of Cardiovascular Diseases,Hypertension Research of Institute,Affiliated Hospital of Zunyi Medical College,Department of Cardiology,Zunyi Medical College,Zunyi Guizhou 563003,China;不详)
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2019年第12期1163-1171,共9页
Chinese Journal of Hypertension
基金
国家自然科学基金资助项目(81160041,81460077)
贵州省国际科技合作计划[G字(2012)7038号]
贵州省优秀科技教育人才省长专项基金项目[黔省专合字(2012)15号].
