Pulmonary hypertension induced by right pulmonary artery occlusion: hemodynamic consequences of Bmpr2 mutation

<bold>Background:</bold> The primary genetic risk factor for heritable PAH is the presence of monoallelic mutations in the <italic>BMPR2</italic> gene. The incomplete penetrance of <italic>BMPR2</italic> mutations implies that additional triggers are necessary for PAH occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, while the redirection of blood flow to unobstructed arteries lead to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers PH in rats with Bmpr2 mutations. <bold>Methods:</bold> <italic>Bmpr2</italic> and WT male and female rats underwent acute and chronic RPAO. They were subjected to hemodynamic characterization, and we examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. <bold>Results:</bold> RPAO induced precapillary PH in male and female rats, both acutely and chronically. <italic>Bmpr2</italic> mutant manifested more severe PH and heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male <italic>Bmpr2</italic> rats. Chronic RPAO resulted in elevated pulmonary <italic>IL-6</italic> and decreased <italic>Gdf2</italic> expression. In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females. <bold>Conclusion:</bold> Our novel rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on sex and gene-related effects.