Upregulation of PDE5 gene expression has been observed in animal models of pulmonary hypertension, and is thought to contribute to vasoconstriction in the lung. Several randomised controlled trials investigating PDE5 inhibitors use in pulmonary arterial hypertension, a subtype of pulmonary hypertension, have demonstrated their potent effects in reducing pulmonary hypertension and vascular remodelling and improving symptoms and mortality in patients with the condition. Long-term treatment with a PDE5 inhibitor has been shown to enhance natriuretic peptide-cGMP pathway, downregulate Ca signaling pathway and alter vascular tone in pulmonary arteries in rat models.