Guimarães C L, Da-Silva S, Couture R, Rae G A
Department of Natural Sciences, Universidade Regional de Blumenau.
J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S371-3. doi: 10.1097/00005344-200036051-00107.
The possible participation of endogenous endothelins (ETs) in enhancement of plasma extravasation induced by oleic acid was assessed in mice. Oleic acid (0.5-2%/kg, i.v.) increased accumulation of Evans blue in lungs in dose-dependent fashion, with a clearcut peak at 1 h (lung Evans blue content: control 0.17 +/- 0.01; oleic acid 1%/kg 0.63 +/- 0.04 microg per 10 mg wet tissue). Pretreatment with the mixed endothelin-ET(A) and ET(B) (ET(A)/ET(B)) receptor antagonist bosentan (30 mg/kg, i.v., 30 min before oleic acid) markedly reduced lung Evans blue content (to 0.24 +/- 0.04), as did pretreatments with prazosin (1 mg/kg), meloxicam (5 mg/kg) and dexamethasone (1 mg/kg/day, for 3 days). Thus, ETs play a pivotal role in the increase in lung microvascular permeability caused by oleic acid in the mouse. The ET receptors involved in the pulmonary vascular changes associated with this experimental model of adult respiratory distress syndrome (ARDS), as well as the relationship between ETs and the sympathetic system, eicosanoids and cytokines remain to be clarified.
在小鼠中评估了内源性内皮素（ETs）在油酸诱导的血浆外渗增强中的可能作用。油酸（0.5 - 2%/kg，静脉注射）以剂量依赖性方式增加肺中伊文思蓝的蓄积，在1小时时出现明显峰值（肺伊文思蓝含量：对照组0.17±0.01；油酸1%/kg为每10毫克湿组织0.63±0.04微克）。用混合的内皮素 - ET(A)和ET(B)（ET(A)/ET(B)）受体拮抗剂波生坦（30毫克/千克，静脉注射，在油酸注射前30分钟）预处理可显著降低肺伊文思蓝含量（降至0.24±0.04），哌唑嗪（1毫克/千克）、美洛昔康（5毫克/千克）和地塞米松（1毫克/千克/天，共3天）预处理也有同样效果。因此，ETs在油酸引起的小鼠肺微血管通透性增加中起关键作用。参与与这种成人呼吸窘迫综合征（ARDS）实验模型相关的肺血管变化的ET受体，以及ETs与交感神经系统、类花生酸和细胞因子之间的关系仍有待阐明。
