Valeric Acid, a Gut Microbiota Product, Lowers Arterial Blood Pressure in Rats.

Abstract

Valeric acid (VA), a short‐chain fatty acid (SCFA), is produced by gut bacteria. The aim of the study was to evaluate if VA affect arterial blood pressure (BP) in rats. Furthermore, we investigated physiological concentrations of VA, and distribution of VA‐D9 to organs involved in the control of the circulatory system after the administration of VA‐D9 into the colon, a major site of microbiota metabolism. Hemodynamics were recorded in anesthetized, male, 14‐week‐old Wistar rats. A vehicle (0.9% NaCl), VA, 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 ex vivo conditions. SCFAs concentration was measured using ultra performance liquid chromatograph with mass spectrometer.Physiological concentration of VA in the colon content was ≈ 650μM and ≈ 0.4μM in systemic blood. VA‐D9 was detected in the liver, the heart, the brain and kidneys 5 min after the administration into the colon. The vehicle did not affect BP and heart rate (HR). VA acid produced a dose‐dependent decrease in BP, and at higher doses decrease in HR. The hypotensive effect of VA was inhibited by the ANT. In vitro, VA dilated GMA and MA. In MA the dilatory effect was reduced by the ANT.In conclusion, VA rapidly penetrates from the colon to systemic tissues exerting a hypotensive effect. The latter is mediated by vasodilation. The hypotensive effect of colon‐derived VA may have a therapeutic potential.Support or Funding InformationThis work was supported by the National Science Centre, Poland grant no. UMO‐2016/21/B/NZ5/02544.