Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration

• Published in: Hypertension research 2022-02, Vol.45 (2), p.270-282
• Main Authors: Wu, Haicui, Lam, Theo Y C, Shum, Tim-Fat, Tsai, Tsung-Yu, Chiou, Jiachi
• Format: Article
• Language: English
• Subjects: Acetates; Animals; Antihypertensives; Blood Pressure; Captopril - pharmacology; Desoxycorticosterone; Digestive system; Gastrointestinal Microbiome; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Microbiota; Rats; Rodents; Salt; Tumor necrosis factor-TNF
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/s41440-021-00796-x

The role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.