Anderson Velasque Catarina, Gisele Branchini, Rafael Andrade Caceres, Renata Streck Fernandes, Bruna Pasqualotto Costa, Kleiton Lima De Godoy Machado, Tiago Becker, Luis Fernando Ferreira, Katya Rigatto, Jarbas Rodrigues de Oliveira, Fernanda Bordignon Nunes
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引用次数: 0
摘要
低血压是全身性炎症的主要特征之一,基本上是由内皮功能障碍引起的。研究表明,氨基酸 L-犬尿氨酸(KYN)会引起哺乳动物血管扩张,导致低血压休克。在低血压休克中,当 KYN 激活时,KCNQ(Kv7)家族基因编码的电压门控钾通道可导致血管扩张。研究认为,1,6-二磷酸果糖(FBP)具有抗炎、抗氧化、免疫调节和调节某些离子通道(Ca2+、Na+ 和 K+)的作用。我们分析了 KYN 和 FBP 对 Wistar 大鼠平均血压(MBP)、收缩压和舒张压(DBP)以及心率变异性(HRV)的影响。结果表明,服用 KYN 能显著降低 MBP、DBP,并增加心率变异性。重要的是,FBP 治疗逆转了 KYN 对 MBP、DBP 和 HRV 的影响。分子对接模拟表明,KYN 和 FBP 的估计结合自由能非常接近,在 KCNQ4 结构中的位置也相同。我们的研究结果表明,FBP 能抑制 KYN 引起的血压下降。研究结果为今后治疗炎症引起的低血压提出了新的假设。
Fructose-1,6-bisphosphate reverses hypotensive effect caused by L-kynurenine in Wistar male rats.
Hypotension is one of the main characteristics of the systemic inflammation, basically caused by endothelial dysfunction. Studies have shown that the amino acid L-kynurenine (KYN) causes vasodilation in mammals, leading to hypotensive shock. In hypotensive shock, when activated by the KYN, the voltage-gated potassium channel encoded by the family KCNQ (Kv7) gene can cause vasodilation. Fructose-1,6-bisphosphate (FBP) it is being considered in studies an anti-inflammatory, antioxidant, immunomodulator, and a modulator of some ion channels (Ca2+, Na+, and K+). We analyzed the effects of KYN and FBP on mean blood pressure (MBP), systolic and diastolic (DBP) blood pressure, and heart rate variability (HRV) in Wistar rats. Results demonstrated that the administration of KYN significant decreased MBP, DBP, and increased HRV. Importantly, the FBP treatment reversed the KYN effects on MBP, DBP, and HRV. Molecular Docking Simulations suggested that KYN and FBP present a very close estimated free energy of binding and the same position into structure of KCNQ4. Our results did demonstrate that FBP blunted the decrease in BP, provoked by KYN. Results raise new hypotheses for future and studies in the treatment of hypotension resulting from inflammation.
期刊介绍:
Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.