The principal findings of the present study are the following: (1) butyrate and acetate restored endothelium-dependent vasodilatation in aortic rings and increased calcium ionophore–stimulated NO production by endothelial cells incubated with AngII; (2) both SCFAs decreased intracellular ROS production from NADPH oxidase and mitochondria; (3) these SCFAs restored the phosphorylation of VASP at Ser239; and (4) GPR-41 and GPR-43 antagonists inhibit the beneficial effects of butyrate in AngII-induced endothelial dysfunction, without affecting acetate effects. The gene discussed is FFAR3; the disease is endothelial dysfunction.