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A short chain fatty acid produced by the gut microbiota plays a role in blood pressure regulation and cardiac contractility

Recent studies by our laboratory and others have highlighted the important role played by short chain fatty acids (SCFA) produced by the gut microbiota and their effect on host physiology. Acetate, the most abundant SCFA present in the blood, has been shown to modulate blood pressure control through at least two mechanisms; renin release in the juxtaglomerular apparatus, and changes in vascular tone in peripheral resistance beds (Pluznick, Protzko et al. 2013). Prior studies by our laboratory have shown that intravenous administration of SCFAs causes acute hypotension in anesthetized mice (Pluznick, Protzko et al. 2013). These prior studies suggested that acetate was acting purely on the peripheral vasculature to cause a vasodilatory effect, as treating vessels with acetate ex‐vivo resulted in relaxation (Natarajan, Hori et al. 2016). To expand upon these findings, here we performed IP injections of acetate in mice that were implanted with DSI telemetry transmitters to monitor blood pressure and heart rate (HR) in real time. Sodium acetate was delivered at a 1g/kg dose via IP, a dose which we have previously found to elevate plasma acetate by 3–4 fold over baseline. This resulted in a rapid and reproducible drop in mean arterial pressure (MAP) (−54.32 +/− 14.20 mmHg maximum drop, n=4, p<0.05) when compared to an IP injection of the same volume of saline. The duration, but not the magnitude of the blood pressure drop was dose dependent based on IP injections of sodium acetate at 0.625 g/kg (27.08 +/− 4.80 minutes to ½ recovery vs 15.57 +/− 7.24 minutes, n=4, p<0.05). Surprisingly, in addition to a significant depression of blood pressure, mice injected with acetate also showed a significant depression in heart rate (−233.50 +/− 101.20 bpm maximum drop, n=4, p<0.05). Preliminary data using combinatory injections of acetate and the vasoconstrictor phenylephrine show a potential attenuation of the blood pressure drop caused by acetate, suggesting a strong vascular component to the physiological effects of acetate. However, had acetate purely been acting on the vasculature, we would have expected heart rate to increase. Lower doses of acetate (0.625g/kg) also yielded a drop in heart rate not significantly different from the 1g/kg dose. To further probe the effects of exogenous acetate administration on specific cardiac functions, pressure volume loops were performed in rats and acetate was administered intravenously at a continuous infusion to provide a steady, measurable effect. Rats treated with acetate showed a significant decrease in cardiac stroke work, developed pressure, and dP/dtmax, and a significant increase in dP/dtmin (n=4, p<0.05), indicating a potential effect on contractility. We hypothesize that acetate acts both on the peripheral vasculature and the cardiac muscle, with both components contributing to the blood pressure and heart rate effects seen in whole animals. Together these data hint at a previously unknown and potentially detrimental effect of short chain fatty acids on cardiac function, and efforts are underway to further what role these effects play in whole organism physiology.