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What are the theories for the cause of primary pulmonary hypertension ?

What are the theories for the cause of primary pulmonary hypertension ? 

• Excess endothelial production of the vasoconstrictor thromboxane relative to dilator prostaglandins
such as prostacyclin.

• 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
and platelets.

• Activation of elastase and matrix metalloprotease enhances production of mitogens.

• Monoclonal proliferation of endothelial cells.

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