Zhu Bo-qing, Sievers Richard E, Browne Amanda E M, Lee Randall J, Chatterjee Kanu, Grossman William, Karliner Joel S, Parmley William W
Department of Medicine, Cardiology Research, VA Medical Center, University of California, San Francisco, 94143-0124, USA.
J Renin Angiotensin Aldosterone Syst. 2003 Mar;4(1):31-7. doi: 10.3317/jraas.2003.005.
We previously showed that an angiotensin-converting enzyme inhibitor (captopril) or an angiotensin receptor blocker (losartan) reduced infarct size and improved endothelial function in a rat model of ischaemia-reperfusion. The present study was undertaken to see if aspirin (ASA) antagonised the beneficial effects of captopril or losartan.
One hundred and fourteen Sprague-Dawley rats were randomised into six groups; Control, ASA, captopril, losartan, ASA+captopril, and ASA+losartan. ASA, captopril or losartan were given at a concentration of 40 mg/kg/day in drinking water. After six weeks of pre-treatment, the rats were subjected to 17 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion, with haemodynamic and ECG monitoring. During the reperfusion period, the effective refractory period (ERP), ventricular fibrillation threshold (VFT) and bleeding time (BT) were measured. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and -independent relaxations were assessed using acetylcholine and nitroglycerin.
Haemodynamic changes were not different between the groups. Serum ASA concentrations were 0.5, 1.1 and 0.6 mg/dl in the ASA, ASA+captopril and ASA+losartan groups, respectively, and BT was prolonged (p<0.01). ASA alone reduced endothelium-dependent relaxation (-29+8 vs. -69+11%, p<0.01), but did not change endothelium-independent relaxation. ASA did not affect endothelial relaxation induced by acetylcholine in the presence of either captopril or losartan. Angiotensin I and ERP were elevated by captopril and losartan. Angiotensin II and VFT were elevated by losartan. ASA with captopril, captopril and losartan equally reduced infarct size, compared with control (39+3, 39+4, and 39+5 vs. 53+3%, all p<0.05).
Captopril and losartan had similar cardiovascular protective effects in a rat model of ischaemia-reperfusion. Aspirin did not attenuate the cardiovascular protective effects of captopril or losartan.
我们之前的研究表明，在缺血再灌注大鼠模型中，血管紧张素转换酶抑制剂（卡托普利）或血管紧张素受体阻滞剂（氯沙坦）可减小梗死面积并改善内皮功能。本研究旨在观察阿司匹林（ASA）是否会拮抗卡托普利或氯沙坦的有益作用。
114只Sprague-Dawley大鼠被随机分为六组：对照组、ASA组、卡托普利组、氯沙坦组、ASA+卡托普利组和ASA+氯沙坦组。将ASA、卡托普利或氯沙坦以40mg/kg/天的浓度加入饮用水中给予大鼠。经过六周的预处理后，对大鼠进行17分钟的左冠状动脉前降支闭塞和120分钟的再灌注，并进行血流动力学和心电图监测。在再灌注期间，测量有效不应期（ERP）、室颤阈值（VFT）和出血时间（BT）。在预先用去氧肾上腺素预收缩的新鲜主动脉环中，使用乙酰胆碱和硝酸甘油评估内皮依赖性和非内皮依赖性舒张。
各组间血流动力学变化无差异。ASA组、ASA+卡托普利组和ASA+氯沙坦组的血清ASA浓度分别为0.5、1.1和0.6mg/dl，且BT延长（p<0.01）。单独使用ASA可降低内皮依赖性舒张（-29+8 vs. -69+11%，p<0.01），但不改变非内皮依赖性舒张。在存在卡托普利或氯沙坦的情况下，ASA不影响乙酰胆碱诱导的内皮舒张。卡托普利和氯沙坦可使血管紧张素I和ERP升高。氯沙坦可使血管紧张素II和VFT升高。与对照组相比，ASA与卡托普利联合使用、卡托普利和氯沙坦均可同等程度地减小梗死面积（39+3、39+4和39+5 vs. 53+3%，均p<0.
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