Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury.

ABSTRACT

OBJECTIVE: To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury. METHODS: Experiments were performed using SD rats, which were divided into three groups control, IH, and SVS group. O2 concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively. RESULTS: Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-ß1 and tumor necrosis factor-alpha in the aorta. CONCLUSION: SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.