What is the mechanism of action of sildenafil (Viagra) in the management of persistent pulmonary hypertension of the newborn?

• A. Nitric oxide antagonist
• B. Phosphodiesterase (PDE5) inhibitor
• C. Selective pulmonary vasodilator
• D. Endothelin receptor blocker

Answer: (B)

The main idea is that sildenafil works by boosting the NO signaling pathway in the pulmonary vessels. In PPHN, the normally high pulmonary vascular tone persists, so increasing relaxation of the pulmonary arteries helps improve oxygenation. Nitric oxide from the endothelium increases cGMP in smooth muscle, causing vasodilation. PDE5 normally breaks down cGMP, but sildenafil inhibits PDE5, raising and prolonging cGMP levels where NO is active. This leads to sustained pulmonary vasodilation and reduced pulmonary vascular resistance. It is not an NO antagonist, not a direct universal vasodilator on its own, and not an endothelin receptor blocker.