Grześk Elżbieta, Szadujkis-Szadurska Katarzyna, Bloch-Bogusławska Elżbieta, Wiciński Michał, Malinowski Bartosz, KołTan Sylwia, Tejza Barbara, Pujanek Maciej, GrześK Grzegorz
Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, PL-85-094 Bydgoszcz, Poland.
Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, PL-85-094 Bydgoszcz, Poland.
Exp Ther Med. 2017 Feb;13(2):766-770. doi: 10.3892/etm.2016.3986. Epub 2016 Dec 19.
It has been demonstrated that 2,4,6-trimethyl--[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C (PLC) and stimulates apoptosis in smooth muscle cells, which may increase vascular reactivity. The primary aim of the present study was to evaluate the physiological effects of the direct stimulation of PLC by m-3M3FBS on vascular smooth muscle reactivity in arteries pre-treated with lipopolysaccharides (LPS) as a model of septic shock. Experiments were performed on isolated and perfused tail arteries of Wistar rats. The contraction force in the model was measured by assessing increases in perfusion pressure at a constant flow. Parameters describing the concentration-response curves (CRCs) obtained for phenylephrine and arginine-vasopressin in the presence of LPS confirmed a decrease in vessels reactivity. In comparison with the controls, m-3M3FBS treatment caused a significant increase in LPS-untreated as well as pre-treated arteries. Furthermore, in the presence of m-3M3FBS, calcium influx from intra- as well as extracellular calcium stores was significantly higher for LPS-untreated and pre-treated arteries. The results of the present study suggested that m-3M3FBS significantly increased the reactivity of vascular smooth muscle cells pre-treated with LPS by increasing the calcium influx from intra- and extracellular calcium stores. Further studies investigating this mechanism are required to evaluate whether this pathway may be a potential therapeutic strategy to treat sepsis.
已证实2,4,6-三甲基--[3-(三氟甲基)苯基]苯磺酰胺(m-3M3FBS)可激活磷脂酶C(PLC)并刺激平滑肌细胞凋亡,这可能会增加血管反应性。本研究的主要目的是评估以脂多糖(LPS)预处理的动脉作为脓毒症休克模型时,m-3M3FBS直接刺激PLC对血管平滑肌反应性的生理影响。实验在Wistar大鼠分离并灌注的尾动脉上进行。通过在恒定流量下评估灌注压力的增加来测量模型中的收缩力。描述在LPS存在下苯肾上腺素和精氨酸加压素获得的浓度-反应曲线(CRC)的参数证实了血管反应性的降低。与对照组相比,m-3M3FBS处理导致未处理以及预处理的动脉均显著增加。此外,在m-3M3FBS存在下,未处理和预处理的动脉从细胞内以及细胞外钙库的钙内流均显著更高。本研究结果表明,m-3M3FBS通过增加细胞内和细胞外钙库的钙内流,显著增加了用LPS预处理的血管平滑肌细胞的反应性。需要进一步研究该机制,以评估该途径是否可能是治疗脓毒症的潜在治疗策略。