Asanuma Hiroshi, Minamino Tetsuo, Sanada Shoji, Ogita Hisakazu, Kim Jiyoong, Fujita Masashi, Hirata Akio, Tsukamoto Osamu, Ogai Akiko, Node Koichi, Hori Masatsugu, Tomoike Hitonobu, Kitakaze Masafumi
Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Prefecture 565-8565, Japan.
J Mol Cell Cardiol. 2005 Oct;39(4):605-14. doi: 10.1016/j.yjmcc.2005.06.013.
Amlodipine reduces oxidative stress that decreases NO and adenosine release. This study was undertaken to examine whether amlodipine mediates coronary vasodilation and improves myocardial metabolism and contractility in ischemic hearts via either adenosine- or NO-dependent mechanisms. In open-chest dogs, amlodipine (2 mug kg per min) was infused at the minimum dose that caused maximal coronary vasodilation. The perfusion pressure was reduced in the left anterior descending coronary artery so that coronary blood flow (CBF) decreased by 50%. Amlodipine increased the difference of the adenosine level (VAD (Ado): 119+/-14 to 281+/-46 nM) and the nitrate+nitrite level (VAD (NOx): 7.8+/-1.3 to 16.1+/-1.1 muM) between coronary venous and coronary arterial blood, and also increased CBF (50+/-3 to 69+/-6 ml/100 g/min). These changes were partially reversed by either 8-sulfophenyeltheophylline (8SPT) or l(omega)-nitro arginine methyl ester (l-NAME), and were completely blocked by both 8SPT and l-NAME. The reduction of CBF increased VAD (8-iso-prostaglandin F(2alpha)), and this increase was reduced by amlodipine (10.8+/-1.1 to 5.0+/-0.5 pg/ml). In addition, pretreatment with superoxide dismutase mimicked the coronary effects of amlodipine and blunted the response to amlodipine administration. Amlodipine-induced coronary vasodilation via both adenosine- and NO-dependent mechanisms. Adenosine and NO may interact in ischemic hearts to mediate coronary vasodilation by amlodipine.
氨氯地平可减轻氧化应激,而氧化应激会减少一氧化氮(NO)和腺苷的释放。本研究旨在探讨氨氯地平是否通过腺苷或NO依赖机制介导缺血心脏的冠状动脉舒张,改善心肌代谢和收缩力。在开胸犬中,以引起最大冠状动脉舒张的最小剂量输注氨氯地平(2微克/千克/分钟)。降低左前降支冠状动脉的灌注压,使冠状动脉血流量(CBF)减少50%。氨氯地平增加了冠状静脉血与冠状动脉血之间腺苷水平的差值(VAD(Ado):从119±14到281±46纳摩尔)和硝酸盐+亚硝酸盐水平的差值(VAD(NOx):从7.8±1.3到16.1±1.1微摩尔),同时也增加了CBF(从50±3到69±6毫升/100克/分钟)。这些变化被8-磺酸苯乙茶碱(8SPT)或左旋硝基精氨酸甲酯(L-NAME)部分逆转,并被8SPT和L-NAME完全阻断。CBF的降低增加了VAD(8-异前列腺素F2α),而氨氯地平可使其增加减少(从10.8±1.1到5.0±0.5皮克/毫升)。此外,超氧化物歧化酶预处理模拟了氨氯地平的冠状动脉效应,并减弱了对氨氯地平给药的反应。氨氯地平通过腺苷和NO依赖机制诱导冠状动脉舒张。腺苷和NO可能在缺血心脏中相互作用,介导氨氯地平引起的冠状动脉舒张。