Role of bradykinin and eNOS in the anti‐ischaemic effect of trandolapril
Role of bradykinin and eNOS in the anti‐ischaemic effect of trandolapril
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缓激肽和 eNOS 在群多普利抗缺血作用中的作用
DOI：
10.1038/sj.bjp.0704052
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发表时间：
2001
影响因子：
7.3
通讯作者：
R. Ferrari
中科院分区：
文献类型：
--
作者：
A. Cargnoni;L. Comini;P. Bernocchi;T. Bachetti;C. Ceconi;S. Curello;R. Ferrari
血管紧张素转换酶(ACE)抑制剂正在研究中，用于治疗缺血性心脏病，其作用机制尚不清楚。研究了曲多普利的抗缺血作用，以及缓激肽对血管内皮细胞组成型一氧化氮合酶(ENOS)的调节作用。研究了三种剂量的在体慢性给药的曲多普利对大鼠全心缺血再灌流后再灌流的影响。曲多普利具有抗脑缺血作用。0.3 mg kg−1可显著降低缺血和再灌流时的舒张压升高(由33.0±4.5降至14.0±5.2 ，P<0.0 5)和再灌流时的舒张压升高(由86.1±9.4降至2 2.2±4.1 ，P<0.0 1)，改善功能恢复，抑制肌酸磷酸激酶的释放，改善再灌流后的能量代谢。Trandolapril下调基线发展压。Trandolapril增加心肌缓激肽含量(从31.8±6.1fmoL/ /gww增加到54.8±7.5fmoL/gww；P<；0.05)和eNOS在主动脉内皮细胞和心肌细胞的表达和活性(从11.3±1.5到17.0±2.0 μg蛋白−1和从0.62±0.05到0.80±0.06 pmoL Prot−1 −1；P<；0.05比对照组)。HOE 140(一种缓激肽B2受体拮抗剂)和NOS抑制剂可抵消上述作用。心肌细胞eNOS表达上调与心肌收缩功能下调呈负相关。我们的研究结果表明，通过缓激肽介导的NO生成增加而下调基础心肌收缩能力，在曲多普利通过减少缺血时的能量分解而发挥抗缺血作用中起着至关重要的作用。
Angiotensin converting enzyme (ACE) inhibitors are under study in ischaemic heart diseases, their mechanism of action being still unknown. The anti‐ischaemic effect of trandolapril and the possible involvement of a bradykinin‐modulation on endothelial constitutive nitric oxide synthase (eNOS) in exerting this effect, were investigated. Three doses of trandolapril, chronically administered in vivo, were studied in isolated perfused rat hearts subjected to global ischaemia followed by reperfusion. Trandolapril has an anti‐ischaemic effect. The dose of 0.3 mg kg−1 exerted the best effect reducing diastolic pressure increase during ischaemia (from 33.0±4.5 to 14.0±5.2 mmHg; P<0.05 vs control) and reperfusion (from 86.1±9.4 to 22.2±4.1 mmHg; P<0.01 vs control), improving functional recovery, counteracting creatine phosphokinase release and ameliorating energy metabolism after reperfusion. Trandolapril down‐regulated the baseline developed pressure. Trandolapril increased myocardial bradykinin content (from 31.8±6.1 to 54.8±7.5 fmol/gww; P<0.05, at baseline) and eNOS expression and activity in aortic endothelium (both P<0.01 vs control) and in cardiac myocytes (from 11.3±1.5 to 17.0±2.0 mUOD μg protein−1 and from 0.62±0.05 to 0.80±0.06 pmol mg prot−1 min−1; both P<0.05 vs control). HOE 140 (a bradykinin B2 receptor antagonist) and NOS inhibitors counteracted the above‐reported effects. There was a negative correlation between myocyte's eNOS up‐regulation and myocardial contraction down‐regulation. Our findings suggest that the down‐regulation exerted by trandolapril on baseline cardiac contractility, through a bradykinin‐mediated increase in NO production, plays a crucial role in the anti‐ischaemic effect of trandolapril by reducing energy breakdown during ischaemia.
血管紧张素转换酶抑制改变血压正常和高血压大鼠中一氧化氮和超氧化物的释放。
DOI：
10.1161/01.hyp.30.5.1183
发表时间：
1997
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Wiemer,G;Linz,W;Hatrik,S;Schölkens,BA;Malinski,T
通讯作者：
Malinski,T