• Excess endothelin-I levels relative to nitric oxide. Inhaled nitric oxide and endothelin-1 antagonists
reduce pulmonary hypertension.
• Excessive thrombosis in situ due to increased platelet activation, plasminogen activator inhibitor
levels and decreased thrombomodulin.
• Increased serotonin levels.
• Inhibition or downregulation of potassium (Kv) channels in pulmonary artery smooth muscle cells
• Activation of elastase and matrix metalloprotease enhances production of mitogens.
• Monoclonal proliferation of endothelial cells.