Involvement of Reactive Oxygen Species in Thrombin-induced Pulmonary Vasoconstriction

Rationale: Pulmonary vascular thrombosis and thrombotic arteriopathy are common pathological findings in pulmonary arterial hypertension. Thrombin may thus play an important role in the pathogenesis and pathophysiology of pulmonary arterial hypertension.Objectives: The present study aimed to elucidate the contractile effect of thrombin in the pulmonary artery and clarify its underlying mechanisms.Methods: The changes in cytosolic Ca2+ concentrations ([Ca2+]i), 20-kD myosin light chain (MLC20) phosphorylation, and contraction were monitored in the isolated porcine pulmonary artery. The production of reactive oxygen species (ROS) was evaluated by fluorescence imaging.Measurements and Main Results: In the presence of extracellular Ca2+, thrombin induced a sustained contraction accompanied by an increase in [Ca2+]i and the phosphorylation of MLC20. In the absence of extracellular Ca2+, thrombin induced a contraction without either [Ca2+]i elevation or MLC20 phosphorylation. This Ca2+- and MLC20 phosphorylatio...