Briyal S, Gandhakwala R, Khan M, Lavhale M S, Gulati A
Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
Physiol Res. 2018 Jun 27;67(Suppl 1):S199-S214. doi: 10.33549/physiolres.933856.
Endothelin-1 (ET-1) acts on ET(A) and ET(B) receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ET(A) and ET(B) receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ET(A) or ET(B) receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ET(A) expression which was attenuated by saline and centhaquin; ET(B) expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ET(A) expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ET(B) expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ET(A) and ET(B) receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy.
内皮素 -1（ET -1）作用于ET(A)和ET(B)受体，与失血性休克（休克）有关。我们确定了休克以及用高渗盐水（盐水）或喷他喹复苏对ET(A)和ET(B)受体表达的影响。将大鼠麻醉，在左股动脉放置压力导管；从右股动脉抽血使平均动脉压（MAP）降至35 mmHg并维持30分钟，然后进行复苏，90分钟后处死大鼠以收集样本进行生化评估。用喷他喹复苏可降低血乳酸水平并提高MAP。休克或复苏后，脑、心、肺和肝中ET(A)或ET(B)受体的蛋白水平未发生改变。在腹主动脉中，休克使ET(A)表达增加（140%），盐水和喷他喹可使其减弱；休克后ET(B)表达未改变，但喷他喹使其增加（79%）。在肾髓质中，休克后ET(A)表达未改变，但喷他喹使其降低（-61%）；休克使ET(B)表达降低（-34%），喷他喹可使其完全恢复，而盐水则无此作用。休克诱导的主动脉和肾髓质中ET(A)和ET(B)受体的变化可被喷他喹逆转，这可能是其发挥疗效的原因。
