期刊
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
卷 14, 期 3, 页码 212-218出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2005.11.006
关键词
nitric oxide synthase inhibitors; mesenteric ischemia-reperfusion; gastrointestinal transit; myeloperoxidase activity; vascular permeability; mice
Nitric oxide (NO) involvement in intestinal ischemia-reperrusion (I/R) injury has been widely suggested but its protective or detrimental role remains still question of debate. Here, we examine the impact of supplementation or inhibition of NO availability on intestinal dysmotility and inflammation caused by mesenteric I/R in mice. Ischemia 45 min and reperfusion 24 h were performed by superior mesenteric artery occlusion in female Swiss mice. Saline-treated sham-operated (S) or normal mice without surgery (N) served as controls. Drugs were subcutaneously injected 0, 4, 8, and 18 11 after ischemia. Upper gastrointestinal transit (GIT, estimated through black marker gavage), intestinal myeloperoxidase activity (MPO), intestinal malondialdehyde levels (MDA), Evans blue extravasation (EB), intestinal histological damage.. and mean arterial pressure (MAP) were considered. In I/R mice, G IT was significantly delayed compared to S and N groups; MPO activity and EB extravasation enhanced, whereas MDA levels did not change. Compared to N and S groups, in I/R mice selective iNOS inhibitor P-BIT significantly prevented motor, MPO and EB changes; putative iNOS inhibitor aminoguanidine significantly counteracted GIT delay but not neutrophil recruitment and the increase in vascular permeability; NOS inhibitor L-NAME and NO precursor L-arginine were scarcely or no effective. Furthermore., in S mice aminoguanidine caused a significant increase of MPO activity reverted by H, histamine receptor antagonist pre-treatment. Unlike P-BIT, aminoguanidine and L-NAME injection increased MAP. These findings confirm a detrimental role for iNOS-derived NO overproduction during reperfusion. Aminoguanidine-associated neutrophil recruitment Suggests that this drug Could act through mechanisms additional to iNOS inhibition involving both eNOS blockade, as indicated by its hemodynamic effects, and indirect activation of H, histamine receptors. (c) 2005 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据