Key result
Irbesartan alleviates high-altitude pulmonary hypertension and LV dysfunction in rats, potentially by regulating intestinal flora.
Why the study?
The possible mechanism of irbesartan in improving high-altitude pulmonary hypertension was explored from the perspective of intestinal bacterial flora.
Does irbesartan improve pulmonary artery pressure and oxidative stress in a rat model of high-altitude pulmonary hypertension?
Does irbesartan improve pulmonary artery pressure and oxidative stress in a rat model of high-altitude pulmonary hypertension?
In a rat model, irbesartan mitigates high-altitude pulmonary hypertension and associated oxidative stress, potentially through modulation of the intestinal microbiome.
OBJECTIVE: High-altitude pulmonary hypertension (HAPH) is one of the diseases with higher occurrence among people living in plateau areas. The possible mechanism of angiotensin II receptor 1 inhibitor irbesartan in improving HAPH was explored from the perspective of intestinal bacterial flora in this study. MATERIALS AND METHODS: A HAPH rat model was established under simulated high-altitude hypobaric hypoxia. The levels of oxidative stress and vasoactive substances were detected after irbesartan intervention, and intestinal flora genomics analysis was performed. RESULTS: High-altitude hypobaric hypoxia-induced the increase in pulmonary artery pressure and left ventricular systolic dysfunction in HAPH model rats, but its effects were alleviated by irbesartan. Changes in the levels of oxidative damage in intestinal tissues, such as the increase in superoxide dismutase and glutathione peroxidase in intestinal tissues and the decrease in malondialdehyde content, were also reversed by irbesartan. The serum levels of angiotensin II, endothelin 1, interleukin-6, and C-reactive protein increased substantially whereas the level of nitric oxide decreased in HAPH model rats. The levels of these vasoconstriction and inflammatory indicators were also reversed after irbesartan intervention. The distribution of intestinal florae in rats was changed by the simulated high-altitude hypoxia environment as manifested by the increased Firmicutes-to-Bacteroidetes ratio (F/B), the increased abundance of Lactobacillaceae and Lachnospiraceae, and the decreased abundance of Prevotellaceae and Desulfovibrionaceae at the family level. However, the changes in F/B ratio and the abundance of these florae were reversed by irbesartan. CONCLUSIONS: Irbesartan can alleviate pulmonary artery pressure and left ventricular relaxation in HAPH model rats, reduce the oxidative damage caused by high-altitude hypoxia, and lower the release of vasoconstrictor factors and inflammatory mediators. These effects might be caused by the increased abundance of Lactobacillaceae and Lachnospiraceae and the decreased abundance of Prevotellaceae and Desulfovibrionaceae in the intestines.
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Nijiati et al. (2021) studied High-altitude pulmonary hypertension (HAPH). Irbesartan vs. HAPH model without intervention was evaluated on Pulmonary artery pressure, left ventricular systolic dysfunction, oxidative stress, and intestinal flora changes. Irbesartan alleviated pulmonary artery pressure and left ventricular dysfunction in a rat model of high-altitude pulmonary hypertension, potentially by regulating intestinal flora.
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