Involvement of reactive oxygen species in thrombin-induced pulmonary vasoconstriction

American Journal of Respiratory and Critical Care Medicine
Jun MakiKatsuya Hirano

Abstract

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. The present study aimed to elucidate the contractile effect of thrombin in the pulmonary artery and clarify its underlying mechanisms. 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. 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 phosphorylation-independent contraction was mimicked by hydrogen peroxide and inhibited by N-acetyl cysteine. Fluorescence imaging revealed thrombin to induce the production of ROS. A Rho-kinase inhibitor, Y27632, inhibited not only the thrombin-induced Ca²(+)- and MLC20 phosphory...Continue Reading

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Citations

Nov 25, 2011·Journal of Applied Physiology·Jian ZhouSteven C George
Jul 9, 2011·American Journal of Respiratory and Critical Care Medicine·Raed A Dweik, Serpil C Erzurum
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Nov 14, 2018·Cardiovascular Research·Yukimitsu KuwabaraKatsuya Hirano
Mar 25, 2019·Cardiovascular Research·Daphne MerkusKarin A Boomars
Jan 18, 2013·American Journal of Physiology. Cell Physiology·Trent ButlerEng-Cheng Chan

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