Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Mol Cell Biochem. 2013 Sep;381(1-2):301-11. doi: 10.1007/s11010-013-1712-9. Epub 2013 Jun 9.
Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas still exist about potential impact of these drugs on cardiovascular system. The present study was aimed to estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA], and SC-560) on oxidative stress in isolated rat heart, with special focus on L-arginine/NO system. The hearts of male Wistar albino rats (total number n = 96, each group 12 rats, 8 weeks old, body mass 180-200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40-120 cmH2O). After control experiments the hearts were perfused with the following drugs: 100 μmol/l ASA (Aspirin), alone or in combination with 30 μmol/l L-NAME, 0.3 μmol/l meloxicam (movalis) with or without 30 μmol/l L-NAME, 3 μmol/l meloxicam (alone or in combination with 30 μmol/l L-NAME), 30 μmol/l L-NAME, and administration of 0.25 μmol/l SC-560. In samples of coronary venous effluent the following oxidative stress markers were measured spectrophotometrically: index of lipid peroxidation (measured as thiobarbituric acid reactive substances [TBARS]), superoxide anion radical release (O2(-)), and hydrogen peroxide (H2O2). While ASA was found to have an adverse influence on redox balance in coronary circulation, and coronary perfusion, meloxicam and SC-560 do not negatively affect the intact model of the heart. Furthermore, all effects were modulated by NOS inhibition. It seems that interaction between COX and L-arginine/NO system truly exists in coronary circulation, and can be one of the possible causes for achieved effects. That means: those effects induced by different inhibitors of COX are modulated by subsequent inhibition of NOS.
尽管环氧化酶 (COX) 抑制剂在临床上得到广泛应用，但关于这些药物对心血管系统潜在影响的问题仍存在争议。本研究旨在评估不同 COX 抑制剂（美洛昔康、乙酰水杨酸 [ASA] 和 SC-560）对分离大鼠心脏氧化应激的影响，特别关注 L-精氨酸/NO 系统。雄性 Wistar 白化大鼠（总数 n = 96，每组 12 只大鼠，8 周龄，体重 180-200g）的心脏按 Langendorff 技术进行逆行灌注，灌注压逐渐升高（40-120cmH2O）。在对照实验后，心脏用以下药物进行灌注：100μmol/L ASA（阿司匹林），单独或与 30μmol/L L-NAME 联合使用，0.3μmol/L 美洛昔康（movalis），单独或与 30μmol/L L-NAME 联合使用，3μmol/L 美洛昔康（单独或与 30μmol/L L-NAME 联合使用），30μmol/L L-NAME，以及 0.25μmol/L SC-560 的给药。在冠状静脉流出物样本中，通过分光光度法测量以下氧化应激标志物：脂质过氧化指数（以硫代巴比妥酸反应物质 [TBARS] 表示）、超氧阴离子自由基释放（O2(-)）和过氧化氢（H2O2）。虽然 ASA 对冠状循环和冠脉灌注的氧化还原平衡有不利影响，但美洛昔康和 SC-560 不会对心脏完整模型产生负面影响。此外，所有作用均受 NOS 抑制的调节。这表明 COX 和 L-精氨酸/NO 系统之间的相互作用确实存在于冠状循环中，可能是产生这些作用的原因之一。这意味着：不同 COX 抑制剂诱导的作用受到随后的 NOS 抑制的调节。
