Valeric acid lowers arterial blood pressure in rats

Valeric acid (VA) is a short-chain fatty acid produced by microbiota and herbs such as Valeriana officinalis. Moreover, VA is released from medicines such as estradiol valerate by esterases. We evaluated the concentrations of endogenous VA in male, 14-week-old rats in the liver, heart, brain, kidneys, lungs, blood and in the colon, a major site of microbiota metabolism, using liquid chromatography coupled with mass spectrometry. In addition, the tissue distribution of VA D9-isotope (VA-D9) administered into the colon was assessed. Finally, we investigated the effect of exogenous VA on arterial blood pressure (BP) and heart rate (HR) in anesthetized rats, and the reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries ex vivo. Physiological concentration of VA in the colon content was ≈650 μM, ≈ 0.1-1 μM in the investigated tissues, and ≈0.4 μM in systemic blood. VA-D9 was detected in the tissues 5 min after the administration into the colon. The vehicle did not affect BP and HR. VA produced a dose-dependent decrease in BP, and at higher doses lowered HR. The hypotensive effect of VA was inhibited by 3-hydroxybutyrate, an antagonist of GPR41/43-receptors but not by the subphrenic vagotomy. Hexamethonium prolonged the hypotensive effect of VA while atropine did not influence the hypotensive effect. VA dilated GMA and MA. In conclusion, the exogenous VA produces vasodilation and lowers BP. The colon-derived VA rapidly penetrates to tissues involved in the control of BP. Further studies are needed to evaluate the effects of endogenous and exogenous VA on the circulatory system.