Knapton A D, Zhang J, Sistare F D, Hanig J P
Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA.
Methods Find Exp Clin Pharmacol. 2010 Sep;32(7):489-97. doi: 10.1358/mf.2010.32.7.1507854.
Exposure of the vasculature to vasodilators, pharmaceuticals and industrial chemicals may lead to injury of the blood vessel wall in animals. Vascular injury may begin with changes in the permeability of vascular endothelial cell and vessels, resulting in possible hemorrhage and edema leading subsequently to immune cell infiltration. The present study was undertaken to determine if the direct exposure of the Sprague Dawley rat mesenteric vasculature through the perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin has any such effects on the blood vessels, and if the two vital dyes Monastral blue B and Evans blue can be used to enhance the visualization of the vascular damage. Microscopic visualization was enhanced by the use of dyes and a variety of alterations of the perfused mesenteric vessels were detected, including varying degrees of mast cell degranulation, microvascular vasodilatation and increased vascular permeability. Macroscopic evidence of vascular damage was minimal. This study demonstrates that in situ perfusion of the rat mesentery is a simple and useful method to eliminate the influence of a variety of physiologic influences or homeostatic responses and can be used to further investigate drug-induced vascular damage.
脉管系统暴露于血管扩张剂、药物和工业化学品下可能会导致动物血管壁损伤。血管损伤可能始于血管内皮细胞和血管通透性的改变,进而可能导致出血和水肿,随后引发免疫细胞浸润。本研究旨在确定通过灌注氨茶碱、非诺多泮、化合物48/80、组胺或5-羟色胺直接暴露于斯普拉格-道利大鼠肠系膜脉管系统是否会对血管产生此类影响,以及两种活性染料酸性蓝B和伊文思蓝是否可用于增强血管损伤的可视化效果。通过使用染料增强了显微镜下的可视化效果,并检测到灌注肠系膜血管的多种变化,包括不同程度的肥大细胞脱颗粒、微血管扩张和血管通透性增加。血管损伤的宏观证据很少。本研究表明,大鼠肠系膜原位灌注是一种简单而有用的方法,可消除各种生理影响或稳态反应的影响,并可用于进一步研究药物诱导的血管损伤。