Bromocriptine significantly reduced right ventricular systolic pressure (P < 0.05) and mitigated right ventricle and pulmonary vascular remodeling in a rat model of pulmonary hypertension.
Does bromocriptine improve hemodynamics and mitigate vascular remodeling in a rat model of pulmonary arterial hypertension?
Bromocriptine improves hemodynamics and mitigates right ventricular and pulmonary vascular remodeling in a rat model of PAH, suggesting a potential new therapeutic direction.
p-value: p=<0.05
Abstract Rationale Bromocriptine has dopaminergic activity and is able to inhibit the secretion of prolactin. It is used to treat prolactin-related menstrual disorders, infertility, and amenorrhea. However, the therapeutic effect of bromocriptine on pulmonary arterial hypertension (PAH) has not been extensively studied.The objective of this study is to explore the therapeutic effect of bromocriptine on pulmonary arterial hypertension and its mechanism of action. Methods In vivo experiments,a single injection of monocrotaline (MCT) was used to establish a PAH rat model. Two weeks after modeling, rats were treated with bromocriptine via intraperitoneal injection for two weeks. Echocardiography was used to assess cardiac function parameters. Right ventricular systolic pressure (RVSP) was measured using right heart catheterization, and pulmonary vascular wall thickness and right ventricular hypertrophy index were assessed using hematoxylin and eosin (HE) staining. In vitro, the 5-Ethynyl-2’-deoxyuridine (EdU) incorporation assay and scratch wound healing assay were performed to determine the effect of bromocriptine on VEGF-induced endothelial cell proliferation and migration, respectively. Results Compared with the model group, the treatment group showed significant improvements in echocardiographic parameters after 14 days of bromocriptine injection in MCT rats. Bromocriptine significantly reduced RVSP (P 0.05), increased cardiac output, and decreased pulmonary vascular resistance (PVR) without affecting heart rate. Additionally, 21 days after MCT administration, the right ventricular hypertrophy index in the treatment group was significantly lower than that in the model group (P 0.05), indicating improved right ventricular and pulmonary vascular remodeling. The wall thickness percentage (WT%) of pulmonary arterioles in the model group was significantly higher than that in the normal control group. The WT% in the treatment group was significantly lower than that in the model group (P 0.05). HE staining of lung tissue showed that the wall thickness of pulmonary vessels in bromocriptine dose group was significantly lower than that in PAH group, the lumen was widened and the inflammation around the vessels was alleviated. Bromocriptine can effectively inhibit MCT-induced thickening of pulmonary arterioles in rats. In vitro experiments demonstrated that bromocriptine significantly inhibited VEGF-induced endothelial cell proliferation and migration (P 0.05). Conclusion Bromocriptine can reduce RVSP, improve hemodynamics, decrease pulmonary vascular resistance and mitigate right ventricle and pulmonary vascular remodeling in rats with pulmonary hypertension. Bromocriptine inhibits VEGF-driven endothelial cell proliferation and migration, confirming its ability to negatively regulate vascular remodeling at the cellular level. Long-term use of bromocriptine can provide a new direction for the treatment of pulmonary arterial hypertension. This abstract is funded by: the Program of National Key Research and Development projects of China (2023YFC2509500) and the Program of National Natural Science Foundation of China (82570413), the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0526700, 2024ZD0528600), the the Pujiang Talent Program (22OHD064), and the Program of Shanghai Pulmonary Hospital (2025-0554-YB-15, LYRC202415).
Zhang et al. (Fri,) conducted a other in Pulmonary arterial hypertension. Bromocriptine vs. Model group was evaluated on Right ventricular systolic pressure (RVSP) (p=<0.05). Bromocriptine significantly reduced right ventricular systolic pressure (P < 0.05) and mitigated right ventricle and pulmonary vascular remodeling in a rat model of pulmonary hypertension.