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.
Highlights
Ample evidence suggests that molecules produced by gut microbiota such as short-chain fatty acids (SCFAs) exert a significant effect on mammalian homeostasis [4, 20]
DMSO, butyric acid (BA), MOPS-PSS, bovine serum albumin (BSA), antagonist of SCFA receptors GPR41/43 (ANT)-3hydroxybutyrate, hexamethonium, and all reagents used to study isolated vessels were purchased from Sigma-Aldrich, Poznan, Poland
A new finding of our study is that BA at a dose which increases the concentration of BA in the colon by 2–3-fold exerts a significant hypotensive effect
Summary
Ample evidence suggests that molecules produced by gut microbiota such as short-chain fatty acids (SCFAs) exert a significant effect on mammalian homeostasis [4, 20]. A hypotensive effect was reported after administration of BA into the kidney medulla [31] and intraperitoneally [25] in rats. Those studies did not evaluate BA blood level and it is difficult to speculate whether the reported effects are of physiological, pharmacological, or suprapharmacological importance
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