Siragy Helmy M, Xue Chun, Webb Randy L
Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, USA.
J Cardiovasc Pharmacol. 2006 May;47(5):636-42. doi: 10.1097/01.fjc.0000211750.01326.b3.
The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3',5'-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-alpha (TNF-alpha) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P < 0.001). Benazepril or amlodipine significantly increased NOX levels (P < 0.05 vs. untreated ischemia), but only benazepril significantly increased cGMP (P < 0.05). Combined benazepril-amlodipine further increased CIF NOX and cGMP (P < 0.001), compared with either drug alone. CIF Ang II and TNF-alpha in sham animals did not change significantly. In animals with ischemia, CIF Ang II and TNF-alpha increased progressively. Amlodipine alone, benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-alpha (P < 0.01 for monotherapies and P < 0.001 for combination therapy). Hydrochlorothiazide did not cause significant changes in NOX, cGMP, or TNF-alpha. Combination benazepril-amlodipine may be beneficial for managing cardiac ischemia.
本研究的目的是确定心肌缺血后心肌炎症是否增加，以及血管紧张素转换酶抑制剂、钙通道阻滞剂或利尿剂是否能降低诱导性心肌缺血大鼠的炎症介质水平。在口服贝那普利、氨氯地平、贝那普利 - 氨氯地平联合用药或氢氯噻嗪的情况下，监测心肌间质液（CIF）中一氧化氮代谢产物（NOX）、环磷酸鸟苷（cGMP）、血管紧张素II（Ang II）和肿瘤坏死因子 - α（TNF - α）的变化。采用微透析技术，在假手术或左前降支冠状动脉闭塞30分钟后，测量几种炎症介质的水平。与假手术动物相比，缺血动物的CIF NOX和cGMP水平降低（P < 0.001）。贝那普利或氨氯地平显著提高NOX水平（与未治疗的缺血组相比，P < 0.05），但只有贝那普利显著提高cGMP（P < 0.05）。与单独使用任何一种药物相比，贝那普利 - 氨氯地平联合用药进一步提高了CIF NOX和cGMP（P < 0.001）。假手术动物的CIF Ang II和TNF - α没有显著变化。在缺血动物中，CIF Ang II和TNF - α逐渐升高。单独使用氨氯地平、单独使用贝那普利或贝那普利 - 氨氯地平联合用药均显著降低TNF - α（单一疗法P < 0.01，联合疗法P < 0.001）。氢氯噻嗪对NOX、cGMP或TNF - α没有引起显著变化。贝那普利 - 氨氯地平联合用药可能对治疗心肌缺血有益。
