Pulmonary hypertension (PH) is a chronic cardiopulmonary disease characterized by pulmonary vascular remodeling and right ventricular hypertrophy, and its pathogenesis is closely associated with the phenotypic switching of macrophages. This study aimed to investigate the effect of hyperuricemia (HUA) on PH by regulating macrophage phenotypes and its underlying mechanism.

A PH rat model was induced using monocrotaline (MCT), and a chronic HUA model was established by combining with potassium oxonate (OA). Benzbromarone (BBR) was used for intervention to reduce uric acid levels. The experiment was divided into four groups: normal control group (CON group), MCT group, MCT+OA group, and MCT+OA+BBR group. After 4 weeks of model establishment, the following parameters were detected in each group of rats: right ventricular hypertrophy index (RVHI); pulmonary arteriole remodeling indicators [percentage of medial thickness to vascular external radius (MT%), percentage of vascular wall area to total vascular area (WA%), percentage of lumen area to total vascular area (VA%)]; macrophage phenotypes in lung tissue [CD68+ total macrophages, CD86+ M1-type macrophages, CD163+ M2-type macrophages]; and the expression levels of inflammatory factors (IL-1β, IL-6, TNF-α, IL-10).

The results showed that compared with the CON group, the RVHI in the MCT group and MCT+OA group was significantly increased (P<0.05); the MT% and WA% of pulmonary arterioles were increased, while VA% was decreased (P<0.05); and the changes in the above indicators were more significant in the MCT+OA group. After BBR intervention, the RVHI, MT%, and WA% in the MCT+OA+BBR group were significantly lower than those in the MCT+OA group (P<0.05). Immunohistochemical results revealed that the expression levels of CD68+ and CD86+ cells in the lung tissue of the MCT+OA group were significantly higher than those in the MCT group (P<0.05), while there was no significant difference in the number of CD163+ cells. Meanwhile, in the MCT+OA group, the expression levels of pro-inflammatory factors (IL-1β, IL-6, TNF-α) were increased, and the expression level of anti-inflammatory factor IL-10 was decreased (P<0.05); after BBR intervention, the levels of the above inflammatory factors were partially reversed (P<0.05).

HUA can aggravate pulmonary vascular remodeling and right ventricular hypertrophy in PH by promoting the polarization of M1-type macrophages and the release of pro-inflammatory factors in lung tissue. Reducing uric acid levels may alleviate the progression of PH by inhibiting the phenotypic switching of M1-type macrophages.