Wang Q D, Hemsén A, Li X S, Lundberg J M, Uriuda Y, Pernow J
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Cardiovasc Res. 1995 Jan;29(1):44-9.
The local myocardial overflow and tissue content of endothelin-like immunoreactivity (ET-LI) during ischaemia and reperfusion as well as the coronary vascular effects of endothelin were characterised in anaesthetised pigs.
Ischaemia was induced by ligation of the left anterior descending coronary artery for 45 min followed by 4 h of reperfusion. ET-LI was analysed in plasma from the anterior interventricular coronary vein and aorta for estimation of local overflow and in myocardial tissue. Endothelin analogues were given in the coronary artery for determination of local vascular effects.
During reperfusion, but not during ischaemia, the veno-arterial concentration difference of ET-LI increased, resulting in a significantly increased overflow at between 10 and 120 min of reperfusion. The tissue concentration of ET-LI in the left ventricle was seven times higher in the ischaemic/reperfused area than in the non-ischaemic area: 161(SEM 30.5) v 25.3(3.8) fmol.g-1, P < 0.05. The increase in myocardial ET-LI was attenuated by 70% (P < 0.01) by coronary venous retroinfusion of the nitric oxide substrate L-arginine, whereas the overflow was unaffected. Chromatographic characterisation of the myocardial ET-LI showed that it was similar to endothelin-1. Intracoronary administration of endothelin-1, endothelin-3, and the endothelin ETB receptor agonist [Ala1,3,11,15]ET-1 evoked dose dependent coronary vasoconstriction, and reductions in left ventricular dP/dt and arterial blood pressure. Endothelin-1 was two times more potent than endothelin-3 and 10 times more potent than [Ala1,3,11,15]ET-1.
Myocardial ischaemia/reperfusion evokes enhanced local overflow of ET-LI during the reperfusion period combined with an increased tissue concentration of ET-LI which is is attenuated by L-arginine. Endothelin evokes potent coronary vasoconstriction via activation of both ETA and ETB receptors.
在麻醉猪身上，对缺血和再灌注期间内皮素样免疫反应性（ET-LI）的局部心肌溢出和组织含量以及内皮素的冠状血管效应进行特征描述。
通过结扎左前降支冠状动脉诱导缺血45分钟，随后再灌注4小时。分析来自室间前冠状静脉和主动脉的血浆中的ET-LI，以估计局部溢出，并分析心肌组织中的ET-LI。将内皮素类似物注入冠状动脉以确定局部血管效应。
在再灌注期间而非缺血期间，ET-LI的静脉-动脉浓度差增加，导致再灌注10至120分钟时溢出显著增加。缺血/再灌注区域左心室的ET-LI组织浓度比非缺血区域高7倍：161（标准误30.5）对25.3（3.8）fmol·g-1，P<0.05。通过冠状动脉静脉逆行输注一氧化氮底物L-精氨酸，心肌ET-LI的增加减少了70%（P<0.01），而溢出不受影响。心肌ET-LI的色谱特征表明它与内皮素-1相似。冠状动脉内给予内皮素-1、内皮素-3和内皮素ETB受体激动剂[Ala1,3,11,15]ET-1可引起剂量依赖性冠状血管收缩，并降低左心室dP/dt和动脉血压。内皮素-1的效力是内皮素-3的两倍，是[Ala1,3,11,15]ET-1的10倍。
心肌缺血/再灌注在再灌注期引起ET-LI局部溢出增强，同时ET-LI组织浓度增加，L-精氨酸可使其减弱。内皮素通过激活ETA和ETB受体引起强烈的冠状血管收缩。
