Renal denervation improves chronic intermittent hypoxia induced hypertension and cardiac fibrosis and balances gut microbiota

Aims: Investigate the effect of renal denervation (RDN) on chronic intermittent hypoxia (CIH) induced high blood pressure (BP) and cardiac injury, and explore whether the effect is associated with gut microbiota alteration and its product, trimethylamine N-oxide (TMAO).

Materials and methods: Thirty six-week-old Sprague Dawley male rats were randomly divided into three groups: Control, CIH (20 cycles h^-1, 7-8% at nadir, 8 h.day^-1 for 6 weeks) and RDN group. Fecal samples, serum and heart tissue were collected at week 6. 16S rRNA gene sequencing was performed in fecal samples.

Key findings: Systolic BP in CIH group was significantly elevated compared with Control (164 ± 3 vs. 143 ± 4 mmHg, p = 0.004), while RDN treatment evidently reduced elevated systolic BP (133 ± 5 vs. 164 ± 3 mmHg, p < 0.001). CIH group featured significant cardiac perivascular fibrosis, compared with Control, whereas RDN treatment effectively attenuated perivascular fibrosis. Principal component analysis showed that CIH rats, but not RDN group were noticeably separated from Control. At phyla level, the structure of the biological community of RDN rats converged with that of control rats, which was apparently different in comparison to CIH rats. TMAO levels in the three groups were not significantly different.

Significance: RDN exerts beneficial effect on BP control and perivascular fibrosis in rats exposed to CIH. This effect is associated with its ability to revert the already skewed gut microbiota caused by CIH, but is not via regulation of TMAO.

Keywords: Blood pressure; Gut microbiota; Obstructive sleep apnea; Renal denervation; Trimethylamine N-oxide.