Brain natriuretic peptide protects against acute pulmonary embolism-induced pulmonary vasoconstriction through natriuretic peptide receptor C.

Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality, driven primarily by a sudden increase in pulmonary artery (PA) resistance. Brain Natriuretic Peptide (BNP) may hold promise for reducing PA resistance. However, its role and mechanism in acute PE are not yet fully understood. This study aims to determine whether BNP alleviates PE-induced pulmonary vasoconstriction by targeting Natriuretic Peptide Receptor C (NPRC) and evaluate its therapeutic potential. Here, we established an acute PE rat model using autologous thrombi, and right ventricle (RV) pressure was monitored to approximate PA resistance. A small group of intermediate-high-risk acute PE patients were observed, who received BNP in addition to anticoagulation, and their clinical outcomes were compared to matched patients receiving anticoagulation alone. BNP at varying doses was administered to optimize therapeutic efficacy in the acute PE rat model. Mechanistic studies assessed BNP's impact on oxidative stress in PA endothelium. In the rats, BNP infusion significantly reduced RV pressure overload and improved survival. Clinically, patients receiving adjunctive BNP experienced more rapid improvement in heart rate, oxygen saturation, and blood pressure stability than anticoagulation alone. BNP decreased NADPH oxidase 2-dependent ROS levels in rats' PA endothelium, thereby reducing myosin light chain phosphorylation in smooth muscle. NPRC, as the central receptor, antagonizes the protective effect of BNP. Collectively, BNP offers a novel choice to mitigate PE-induced pulmonary vasoconstriction via NPRC-mediated mechanisms, which support BNP's therapeutic potential for intermediate-high-risk PE.