Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors

Pflugers Arch. 2019 Dec;471(11-12):1441-1453. doi: 10.1007/s00424-019-02322-y. Epub 2019 Nov 15.

Abstract

Butyric acid (BA) is a short-chain fatty acid (SCFA) produced by gut bacteria in the colon. We hypothesized that colon-derived BA may affect hemodynamics. Arterial blood pressure (BP) and heart rate (HR) were recorded in anesthetized, male, 14-week-old Wistar rats. A vehicle, BA, or 3-hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered intravenously (IV) or into the colon (IC). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested ex vivo. The concentration of BA in stools, urine, portal, and systemic blood was measured with liquid chromatography coupled with mass spectrometry. BA administered IV decreased BP with no significant effect on HR. The ANT reduced, whereas L-NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of BA. In comparison to BA administered intravenously, BA administered into the colon produced a significantly longer decrease in BP and a decrease in HR, which was associated with a 2-3-fold increase in BA colon content. Subphrenic vagotomy and IC pretreatment with the ANT significantly reduced the hypotensive effect. Ex vivo, BA dilated MA and GMA. In conclusion, an increase in the concentration of BA in the colon produces a significant hypotensive effect which depends on the afferent colonic vagus nerve signaling and GPR41/43 receptors. BA seems to be one of mediators between gut microbiota and the circulatory system.

Keywords: Bacterial metabolites; Blood pressure; Butyric acid; SCFA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects*
  • Arteries / drug effects
  • Arteries / metabolism
  • Butyric Acid / pharmacology*
  • Colon / drug effects*
  • Colon / metabolism
  • Fatty Acids, Volatile / pharmacology
  • Gastrointestinal Microbiome / physiology*
  • Heart Rate / drug effects
  • Hypotension / drug therapy
  • Hypotension / metabolism
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Vagus Nerve / drug effects*
  • Vagus Nerve / metabolism

Substances

  • Fatty Acids, Volatile
  • Ffar2 protein, rat
  • Gper1 protein, rat
  • Receptors, G-Protein-Coupled
  • Butyric Acid
  • NG-Nitroarginine Methyl Ester