Gut microbiota-derived short chain fatty acids stimulate mesenteric artery vasodilation

Abstract

Authors: SN Menon, F Zerin, AK Pandey, T Rahman, and R Hasan Accumulating evidence suggests that gut microbiota-derived short-chain fatty acids (SCFA's) such as acetate, propionate and butyrate have beneficial effects on the cardiovascular system. However, whether these SCFAs can directly influence arterial contractility remains unclear. Here, we sought to examine the effects of sodium acetate and propionate on the contractility of resistance mesenteric arteries from Sprague Dawley rats, and characterize their mechanism of action. Our pressurized artery myography data showed that both acetate and propionate produced a concentration-dependent vasodilation in mesenteric arteries. Our data also showed that co-application of L-NNA, a selective inhibitor of endothelial nitric oxide synthase (eNOS), with acetate caused 35% reversal of acetate-evoked vasodilation, suggesting that additional vasodilatory mechanisms, including those of smooth muscle origin may be involved. On the other hand, co-application of L-NNA with propionate caused no reversal of sodium propionate-evoked vasodilation, precluding the role of endothelial nitric oxide production. Altogether, our data unveils a novel role for SCFA's in producing direct systemic mesenteric artery vasodilation, which is likely to be mediated by both endothelium- and smooth muscle-specific vasodilatory signaling. Future studies will be focused on dissecting the detailed mechanisms for SCFA-induced mesenteric artery vasodilation, and its relevance for systemic blood pressure regulation.