Indole and indoxyl sulfate, gut bacteria metabolites of tryptophan, change arterial blood pressure via peripheral and central mechanisms in rats

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 D1, D2, α1 and 5 HT2A receptor blocker; pizotifen, a non-selective 5-HT1, 5-HT2A and 5HT2C receptor blocker; and ondansetron, a 5-HT3 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.

Keywords: Arterial blood pressure; Gut bacteria; Indole; Metabolites; Serotonin receptors; cis-(Z)-flupenthixol dihydrochloride; indole (1H-indole); indoxyl sulfate (potassium 1H-indol-3-yl sulfate); ondansetron; pizotifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects*
  • Gastrointestinal Microbiome*
  • Indican / pharmacology*
  • Indoles / pharmacology*
  • Infusions, Intravenous
  • Infusions, Intraventricular
  • Male
  • Rats, Wistar
  • Serotonin / metabolism
  • Tryptophan / metabolism


  • Indoles
  • Serotonin
  • indole
  • Tryptophan
  • Indican