Abstract
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.
Highlights
It has been shown that captopril-induced reduction in blood pressure was associated with the gut-brain axis, in which captopril was given to SHRs followed by monitoring the changes in the gut microbiota and neuronal activity [43]
The aging factor was ignored during captopril treatment
To the best of our knowledge, this is the first report showing that the antihypertensive drug captopril rebalances the changes in the gut microbiota in a DOCA-salt-induced hypertensive rat model
Summary
The gut microbiota, as an “essential organ” in humans, harbors approximately 150 times more genes than those found in the entire human genome [1, 2]. Increasing evidence indicates that the gut microbiota within humans plays crucial roles in human health and diseases, including obesity [3], colorectal cancer [4], liver cirrhosis [5], arthritis [6], and type 2 diabetes [7]. The gut microbiota is associated with energy harvesting by extracting energy from food and could promote obesity [8]. Many metabolic genes found in the gut microbiota encode unique and specific enzymes that are involved in different biochemical pathways in humans [9]. The gut microbiota protects its host from infection by foreign pathogens via various strategies, such as providing physical barriers and immunomodulation [10]
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