COX-2抑制剂尼美舒利通过改善内皮功能和增加NO对抗大鼠心脏氧化应激损伤.pdfVIP

674 Acta Physiologica Sinica , October 25, 2007, 59 (5): 674-680 Research Paper COX-2 inhibitor nimesulide protects rat heart against oxidative stress by improving endothelial function and enhancing NO production LV Ping-Ping, FAN Ying, CHEN Wen-Liang, SHEN Yue-Liang, ZHU Li, WANG Lin-Lin, CHEN Ying-Ying* Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China Abstract: Since a cyclooxygenase 2 (COX-2) inhibitor can reduce infarct size and improve contractility in ischemic myocardium, the aim of the present study was to explore whether COX-2 inhibitor nimesulide could protect myocardial function against oxidative stress injury in rat hearts, and to investigate the underlying mechanisms. The isolated rat hearts perfused by Langendorff method were exposed to 140 µmol/L of H O , and the cardiac contractility was measured. Then, the responses of coronary arteries, precontracted 2 2 with U-46619, to the endothelium-dependent vasodilator serotonin (5-HT) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were evaluated. The results were as follows: (1) In hearts exposed to H O for 20 min, the left ventricular 2 2 developed pressure [LVDP, (54.8±4.0)%] and maximal rate of rise/fall of ventricular pressure [±dp /dtmax, (50.8±3.1)% and (46.2±2.9)%] were reduced compared with that in the control group (100%). After pretreatment with nimesulide (5 µmol/L) for 10 min before H2O2 perfusion, LVDP and ±dp /dtmax were enhanced to (79.9±2.8)%, (80.3±2.6)% and (81.4±2.6)%, respectively (P0.01), and this was partially abolished by the nitric oxide synthase (NOS) inhibitor L -NAME