Sucralose and Acesulfame K modulate human and rodent vascular smooth muscle contractility independently of the presence of the sweet taste receptor. A study of the SOSweet project

Introduction Originally thought to be physiologically inert, artificial sweeteners are more and more recognized to alter various biological functions through their interaction with the sweet taste receptor in extraoral sites. Alarmingly, recent epidemiological data have shown that frequent consumption of artificial sweeteners (AS) is associated with an increased risk of vascular events. However, to date, no studies have tested the hypothesis that AS might directly impact the vasculature. Objective The aim is to characterize the effect of the highly consumed AS, Sucralose and Acesulfame K (AceK), on the vascular wall. The specific objective of the present study is to focus on the vasomotor function. Methods Biomolecular and functional investigations were performed on isolated rodent aortas, human dermal micro-arteries and omental arteries. Ex-vivo vasomotor function was assessed using isometric tension measurements in an organ bath system. Results Our preliminary data show that mRNA of both T1R2 and T1R3, the two subunits of the sweet taste receptor, are expressed in the vascular wall. Cumulative addition of AceK or sucralose revealed that high concentration (10 mM) of these molecules exert respectively vasoconstrictive and vasorelaxant properties on both rodent and human arteries. Lower concentrations (1 mM) of AceK were associated with an exacerbated vasoreactivity to the α1 adrenergic agonist phenylephrine. All these effects were independent of the presence of the endothelium. Surprisingly, T1R inhibition with gurmarin, as well as T1R3 invalidation (KO mice), had no consequence on sucralose and AceK vasoactive effects. Conclusion Our work first show that AS can modulate smooth muscle vascular tone. The in-vivo significance and molecular mechanisms involved remain to be determined. Future investigations will also address other vascular functions to better understand the possible consequences of AS consumption on the cardiovascular system.