School of Medicine of Ribeirão Preto, University of São Paulo-USP, Brazil.
Vascul Pharmacol. 2011 Jan-Feb;54(1-2):44-51. doi: 10.1016/j.vph.2010.12.002. Epub 2010 Dec 15.
Nitric oxide has been pointed out as the main agent involved in the vasodilatation, which is the major symptom of septic shock. However, there must be another mediator contributing to the circulatory failure observed in sepsis. This study aimed to investigate the endothelium-dependent relaxation induced by acetylcholine and the factors involved in this relaxation, using aortic rings isolated from rats submitted to cecal ligation and perforation (CLP), 2h after induction of sepsis, which characterizes the hyperdynamic phase of sepsis. Under inhibition of constitutive NO-synthases (cNOS), the relaxation induced by acetylcholine was greater in the aortic rings of rats submitted to CLP compared with sham-operated rat aortic rings. The cyclooxygenase inhibitor indomethacin normalized this response, and the concentration of the stable metabolite of prostacyclin in the aorta of CLP rats increased in basal conditions and after stimulation with acetylcholine. Acetylcholine-induced NO production was lower in the endothelial cells from the aorta of CLP rats compared with sham rat aorta, but the protein expression of the cNOS was not altered. Moreover, iNOS protein expression could not be detected. Therefore, prostacyclin, and not only nitric oxide, is a mediator of the vasorelaxation induced by acetylcholine in aortas from rats submitted to CLP.
一氧化氮被指出是参与血管舒张的主要物质，而血管舒张是感染性休克的主要症状。然而，在败血症中观察到的循环衰竭，一定还有其他介质参与其中。本研究旨在探讨腹主动脉结扎和穿孔（CLP）后 2 小时诱导败血症的大鼠分离的主动脉环中，乙酰胆碱诱导的内皮依赖性松弛及其涉及的因素，该模型特征为败血症的高动力期。在抑制组成型一氧化氮合酶（cNOS）后，与假手术大鼠主动脉环相比，CLP 大鼠的主动脉环中乙酰胆碱诱导的松弛作用更大。环加氧酶抑制剂吲哚美辛使这种反应正常化，CLP 大鼠主动脉中环前列腺素的稳定代谢产物的浓度在基础条件下和乙酰胆碱刺激后增加。与假鼠主动脉相比，CLP 大鼠主动脉内皮细胞中乙酰胆碱诱导的一氧化氮生成较低，但 cNOS 的蛋白表达没有改变。此外，不能检测到诱导型一氧化氮合酶的蛋白表达。因此，前列腺素，而不仅仅是一氧化氮，是 CLP 大鼠主动脉中乙酰胆碱诱导血管舒张的介质。
