Kurata C, Callahan R J, Molea N, Wilkinson R, Fischman A J, Strauss H W
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
Eur J Pharmacol. 1995 Jul 1;293(2):109-14. doi: 10.1016/0926-6917(95)00005-4.
Endothelin-1 is a potent vasoconstrictor. This study was performed to determine whether arterial injury, induced by either hypercholesterolemia or mechanical disruption of the endothelium, is associated with increased localization of endothelin-1 in the artery. The blood clearance and tissue distribution of intravenously injected [125I]endothelin-1 was evaluated in 33 rabbits--control animals (n = 7), balloon de-endothelialized animals (n = 12), cholesterol-fed animals (n = 6) and animals that had both balloon de-endothelialization and high cholesterol diet (n = 8). The blood clearance half time was less than 10 min, with slightly slower clearance in the ballooned/cholesterol-fed animals. [125I]Endothelin-1 localized in the lung (approximately 12% injected dose (ID)/organ) and kidney (approximately 8%ID/organ). [125I]Endothelin-1 localization in the injured aorta increased from the baseline level of 0.06%kgID/g to its highest level within 5 min of balloon de-endothelialization (0.2%kgID/g) and decreased to 0.11%kgID/g within one week and remained essentially unchanged through 16 weeks. The area with increased binding of [125I]endothelin-1 corresponded to the zone of arterial injury stained with Evans blue. On the other hand, the binding in the aorta did not increase with the atherogenic diet. These findings suggest that endothelin-1 accumulates in injured vessels, attaining the highest levels immediately after mechanical injury.
内皮素 -1是一种强效血管收缩剂。本研究旨在确定由高胆固醇血症或内皮机械性损伤所诱导的动脉损伤是否与动脉中内皮素 -1定位增加有关。在33只兔子中评估了静脉注射[125I]内皮素 -1的血液清除率和组织分布——对照组动物（n = 7）、球囊去内皮动物（n = 12）、喂胆固醇动物（n = 6）以及既接受球囊去内皮又接受高胆固醇饮食的动物（n = 8）。血液清除半衰期小于10分钟，在球囊扩张/喂胆固醇的动物中清除稍慢。[125I]内皮素 -1定位于肺（约为注射剂量（ID）的12%/器官）和肾（约为8%ID/器官）。[125I]内皮素 -1在损伤主动脉中的定位从基线水平0.06%kgID/g在球囊去内皮后5分钟内升至最高水平（0.2%kgID/g），并在一周内降至0.11%kgID/g，在16周内基本保持不变。[125I]内皮素 -1结合增加的区域与伊文思蓝染色的动脉损伤区域相对应。另一方面，主动脉中的结合并未随致动脉粥样化饮食而增加。这些发现表明内皮素 -1在受损血管中蓄积，在机械损伤后立即达到最高水平。
