Wood J G, Zhang Q, Yan Z Y, Cheung L Y
Department of Surgery, University of Kansas Medical Center, Kansas City 66160, USA.
Am J Physiol. 1996 Jul;271(1 Pt 1):G27-35. doi: 10.1152/ajpgi.1996.271.1.G27.
We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction is enhanced after ischemia-reperfusion. The purpose of our present study was to examine the role of nitric oxide in regulating ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion. Using a mechanically perfused stomach segment from chloralose-anesthetized dogs, we examined 1) responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate {1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor} attenuates the augmented response to ET-1 after ischemia-reperfusion. Our results show that 1) L-NAME significantly increased baseline vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstrictor response to ET-1 after ischemia-reperfusion. Our findings are consistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal conditions, and loss of this vasodilator after ischemia-reperfusion results in an augmented response to ET-1.
我们之前观察到，内皮素-1（ET-1）诱导的胃血管收缩在缺血再灌注后会增强。我们当前研究的目的是检测一氧化氮在正常条件下以及缺血再灌注后调节ET-1诱导的血管收缩中的作用。使用来自水合氯醛麻醉犬的机械灌注胃段，我们检测了：1）单独使用N-硝基-L-精氨酸甲酯（L-NAME）以及与L-精氨酸联合使用时的反应；2）L-NAME在正常条件下和缺血再灌注后是否影响ET-1诱导的血管收缩；3）精胺NONOate{1,3-丙二胺-N-[4-1-(3-氨基丙基)-2-羟基-2-亚硝基肼基]丁基；一种一氧化氮供体}是否能减弱缺血再灌注后对ET-1增强的反应。我们的结果显示：1）L-NAME显著增加基线血管阻力，且L-精氨酸可减弱此反应；2）L-NAME增强了ET-1诱导的血管收缩；3）在再灌注期间给予精胺NONOate在很大程度上减弱了缺血再灌注后对ET-1的血管收缩反应。我们的发现与以下假设一致，即一氧化氮在正常条件下调节对ET-1的反应，且缺血再灌注后这种血管舒张剂的丧失导致对ET-1的反应增强。
