Carotid baroreceptor stimulation attenuates obesity-related hypertension through sympathetic-driven IL- 22 restoration of intestinal homeostasis.

Abstract

BACKGROUND: Gut microbiota and its metabolites, as well as the intestinal barrier, play important roles in the development of obesity-related hypertension. Sympathetic nerves are critical for intestinal homeostasis. Carotid baroreceptor stimulation (CBS) has been shown to exert protective effects against hypertension via sympathetic tone reduction. This study aimed to reveal the effects of CBS treatment on intestinal homeostasis and its underlying mechanisms in obesity-related hypertension. METHODS: An animal model of obesity-related hypertension was established with Sprague-Dawley rats by a high-fat diet and 10% fructose solution for 13 weeks. CBS devices were implanted at the 5 th week. The effects of CBS on body weight, blood pressure, gut microbiota, intestinal autonomic nerve, intestinal barrier, and type 3 innate lymphoid cells (ILC3 s) were investigated. RESULTS: CBS treatment significantly reduced blood pressure and body weight in rats with obesity-related hypertension. In addition, CBS obviously improved gut microbial dysbiosis and intestinal barrier damage. Interestingly, after an 8-week CBS intervention, the obesity-related hypertensive rats exhibited a dramatic decrease in sympathetic nerve distribution and norepinephrine concentration, as well as an increase in IL- 22 production by ILC3 s in the intestine. CONCLUSIONS: CBS increased IL- 22 production in ILC3 s to alleviate gut microbial dysbiosis and intestinal barrier destruction, thus improving obesity-related hypertension in rats.