In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms.
The aim of this study was to investigate the effects of urocortin (UCN) on oxidative stress and the mechanisms of urocortin on ischemia-reperfusion injury in vivo in the rat model. Thirty-six Sprague-Dawley rats were divided into 6 groups, including sham, control (normal saline solution), UCN1, UCN2, UCN3, and verapamil groups. The left anterior descending coronary artery of all rats except those in the sham group was treated with a 30-min occlusion followed by a 60-min reperfusion. Just before the occlusion, normal saline solution, UCN (5, 10, and 20 microg/kg body mass), or verapamil (1 mg/kg body mass) was administered. Heart rates, beating rhythm, and S-T segments were constantly monitored using an ECG. At the completion of the drug administration, blood samples were taken to measure the activity of superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-PX), and nitric oxide (NO) to evaluate the effects of UCN on oxidative stress. Finally, the size of infarction was measured. Arrhythmia rates were significantly lower, and the infarction size was significantly smaller (p < 0.01), in the UCN groups vs. the control group. Verapamil also significantly reduced arrhythmia rates and infarction size. The MDA activities were remarkably diminished, whereas the SOD, GSH-PX, and NO activities were significantly higher in the UCN and VER groups (p < 0.01). MDA, SOD, and NO activities were strongly correlated with UCN doses. These results suggest that UCN may play a protective role in ischemia-reperfusion injury in rat hearts against the oxidative stress by inhibiting free radicals' activities.
Liu
Chun-Na
CN
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Yang
Cui
C
Liu
Xin-Yu
XY
Li
Shengnan
S
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005609:Free Radicals / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D054832:Urocortins
D002316:Cardiotonic Agents; D005609:Free Radicals; D008054:Lipid Peroxides; D054832:Urocortins; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase