Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Pharmacol Res. 2018 Apr;130:172-179. doi: 10.1016/j.phrs.2017.12.025. Epub 2017 Dec 26.
Arterial blood pressure (BP) is regulated by a complex network of peripheral and central (brain) mechanisms. Research suggests that gut bacteria-derived compounds may affect the circulatory system. We evaluated hemodynamic effects of indole, a gut bacteria-derived product of tryptophan, and indoxyl sulfate (indoxyl), a liver metabolite of indole. BP and heart rate (HR) were recorded in anesthetized, male, Wistar rats at baseline and after the administration of either a vehicle, indole, or indoxyl into the femoral vein (IV) or into the lateral ventricle of the brain (ICV). Besides, we evaluated the effect of pretreatment with flupentixol, a non-selective D, D, α and 5 HT receptor blocker; pizotifen, a non-selective 5-HT, 5-HT and 5HT receptor blocker; and ondansetron, a 5-HT blocker, on hemodynamic responses to indole and indoxyl. Vehicle infused IV and ICV did not affect hemodynamics. Indole administered IV produced a dose-dependent increase in BP but not HR. In contrast, the ICV infusion of indole produced a decrease in BP and HR. Indoxyl infused IV produced an increase in BP and HR, whereas indoxyl infused ICV did not affect BP and HR. The hemodynamic effects of indole and indoxyl were inhibited by pretreatment with ondansetron and pizotifen but not flupentixol. In conclusion, indole and indoxyl sulfate affect arterial blood pressure via peripheral and central mechanisms dependent on serotonin signalling. We propose that indole and indoxyl sulfate may be mediators in the interaction between gut bacteria and the circulatory system.
动脉血压（BP）受外周和中枢（大脑）机制的复杂网络调节。研究表明，肠道细菌衍生的化合物可能会影响循环系统。我们评估了色氨酸衍生的肠道细菌产物吲哚和吲哚硫酸盐（吲哚）作为肝脏吲哚代谢物对血流动力学的影响。在麻醉的雄性 Wistar 大鼠中，在股静脉（IV）或侧脑室（ICV）给予载体、吲哚或吲哚硫酸盐后，记录 BP 和心率（HR）。此外，我们评估了氟哌啶醇（一种非选择性 D、D、α和 5-HT 受体阻滞剂）、匹莫齐特（一种非选择性 5-HT、5-HT 和 5-HT 受体阻滞剂）和昂丹司琼（一种 5-HT 阻滞剂）预处理对吲哚和吲哚硫酸盐引起的血流动力学反应的影响。IV 和 ICV 输注载体不影响血液动力学。IV 给予吲哚可剂量依赖性地增加 BP，但不增加 HR。相反，ICV 给予吲哚可降低 BP 和 HR。IV 给予吲哚可增加 BP 和 HR，而 ICV 给予吲哚硫酸盐不影响 BP 和 HR。昂丹司琼和匹莫齐特预处理可抑制吲哚和吲哚硫酸盐的血流动力学作用，但氟哌啶醇预处理则无影响。总之，吲哚和吲哚硫酸盐通过依赖于 5-HT 信号的外周和中枢机制影响动脉血压。我们提出，吲哚和吲哚硫酸盐可能是肠道细菌与循环系统相互作用的介质。
