Butyric Acid, a Gut Bacteria‐Produced Metabolite, Decreases Arterial Blood Pressure via a Gut‐Vagus Nerve Signaling in Rats

Abstract

Butyric acid (BA) is one of several short‐chain fatty acids (SCFAs) produced by gut microbiota. The aim of the study was to evaluate if BA may exert hemodynamic effects via an afferent gut‐nervous system signalling. Hemodynamics were recorded in male, 14‐week‐old, anesthetized, Wistar rats. A vehicle (0.9% NaCl), BA, or 3‐hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered into the colon (IC) or intravenously (IV). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested in vitro. SCFAs concentration was measured using ultra performance liquid chromatograph with mass spectrometer. Physiological BA concentration in the colon content (stools) was ≈ 9mM but 1000‐fold lower in systemic venous blood. The vehicle and ANT did not affect arterial blood pressure (BP) and heart rate (HR). BA administered IC produced 2–3‐fold increase in BA colon content and a prolonged decrease in BP and HR, with no significant changes in QTc, a marker of cardiotoxicity. Intestinal blood flow was not affected. Subphrenic vagotomy and IC pretreatment with ANT significantly reduced the hypotensive effect of IC BA. The hypotensive effect was also reduced by IV administered hexamethonium but not by atropine. BA administered IV produced shorter decrease in BP than BA administered IC, and did not affect HR. The ANT reduced, whereas L‐NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of IV BA. In vitro, BA dilated MA and GMA at concentrations 10–20‐fold higher than physiological concentration of BA in systemic blood. In conclusion, at physiological concentration the colon appears the most likely site of BA action. An increase in colonic BA lowers BP. This seems to be mediated by vagal signaling and GPR41/43.Support or Funding InformationSupported by the National Science Centre, Poland grant no. UMO‐2016/22/E/NZ5/00647This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.