美托洛尔和卡维地洛对肾血管性高血压的血压及心室重构的干预作用  

Intervention effects of metoprolol and carvedilol in lowering blood pressure and ventricular remodeling in rat models with renovascular hypertension

作　　者：刘娟[1] 刘海[1] 汤永谦[1] 董定军 LIU Juan;LIU Hai;TANG Yongqian(Department of Cardiology,Central Hospital of Xiangyang City,Hubei,Xiangyang 441020,China)

机构地区：[1]湖北省襄阳市中心医院(湖北文理学院附属医院)心内科,441020

出　　处：《河北医药》2018年第15期2245-2250,共6页Hebei Medical Journal

摘　　要：目的探讨卡维地洛和美托洛尔对肾血管性高血压的降压效应及心室重塑的干预作用。方法建立肾血管性高血压大鼠模型,随机分成单纯手术组、卡维地洛组、美托洛尔组、卡(卡维地洛)+L(一氧化氮合酶NOS抑制剂,L-NAME)组和假手术组。药物干预8周后采用HE及MASSON染色,观察病理学形态,并计算左心室质量指数(LVMI)、心肌胶原容积分数(CVF)及心肌血管周围胶原面积分数(PVCA);采用硝酸还原法测定血浆一氧化氮(NO)的水平,放免法测定血浆内皮素(ET)、降钙素基因相关肽(CGRP)的含量。结果改良缩窄大鼠左肾动脉方法可以形成稳定的肾血管性高血压模型,术后4周平均收缩压(SBP)高于160 mm Hg,3组药物干预大鼠组血压明显下降,但未降至假手术组水平(P<0.05);HE染色可见3组药物干预组得到改善,卡+L组仍有较多炎性细胞参与;MASSON染色可见3组药物干预组仍有部分蓝色胶原存在;卡维地洛组、美托洛尔组、卡+L组CVF降低,但未降至假手术组水平(P<0.01),卡+L组CVF高于卡维地洛组(P<0.01);卡维地洛组、美托洛尔组大鼠PVCA下降,并未降至假手术组水平(P<0.01),卡+L组PVCA较单纯手术组并未下降,并高于卡维地洛组(P<0.01);卡维地洛组较单纯手术组NO明显升高(P<0.01),与假手术组无明显差别(P>0.05),卡+L组NO水平低于卡维地洛组(P<0.01),美托洛尔组NO水平较单纯手术组有所上升(P<0.05),但仍低于卡维地洛组(P<0.01);卡维地洛组、美托洛尔组ET水平低于单纯手术组(P<0.01),卡+L组ET含量高于卡维地洛组(P<0.01),较单纯手术组没有差异(P>0.05);肾动脉缩窄4组大鼠血浆CGRP水平较假手术组均有上升,美托洛尔组低于卡维地洛组(P<0.05)。结论肾动脉缩窄能够形成左室重构模型,卡维地洛、美托洛尔均能改善左室重构,卡维地洛的作用可能在一定程度上与NO系统相关。Objective To investigate the intervention effects of metoprolol and carvedilol in lowering blood pressure and ventricular remodeling in rat models with renovascular hypertension. Methods The SD rat models with renovascular hypertensive model were established by narrowing left renal artery,then the successful models were randomly divided into simple operation group,carvedilol group,metoprolol group,C ＋ L（carvedilol ＋ NOS depressor-L-NAME） group,and sham operation group. After 8-week phamacological intervention,the changes of pathologic morphous were observed by hematoxylin-eosin（HE） and MASSON staining,and the left ventricular mass index（LVMI）,collagen volume fraction（CVF） and perivscular collagen area（PVCA） score were calculated and compared among the five groups. Moreover the NO levels were measured by nitrate reduction method and the levels plasma endothelin（ET）,calcitonin generelated peptide（CGRP） were detected by radioimmunoassay. Results The improved renal artery coarctation of rats could induce stable renovascular hypertension animal models. At 4 weeks after operation,the average systolic blood pressure（SBP） was more than 160 mm Hg,and blood pressure levels in the three pharmacological intervention groups were obviously dcreased,however,which were not decreased to the levels in sham-operation group（P〈 0. 05）. HE staining showed there were myocardial cell hypertrophy,myofiber disorders,inflammatory cell infiltration in simple operation group,and ameliorated symptoms in three drup intervention groups. but there were still considerable inflammatory cells in C ＋ L group. MASSON staining showed there were still partly blue collagen deposition in three intervention groups. The CVF in carvedilol group,metoprolol group and C ＋ L group was significantly decreased（P〈 0. 01）,however,which was not decreased to the levels in sham-operation group. Moreover CVF in C ＋ L group was higher than that in carvedilol group（P〈 0. 01）. PVCA in carvedilol group and metopro

关 键 词：肾血管性高血压 左心室重构 卡维地洛 美托洛尔 一氧化氮合酶NOS抑制剂 

分 类 号：R544.14[医药卫生—心血管疾病]