Sildenafil treats pulmonary arterial hypertension (PAH) by selectively inhibiting phosphodiesterase type 5 (PDE5). This enzyme normally breaks down cyclic guanosine monophosphate (cGMP), a crucial molecule for vascular smooth muscle relaxation. By blocking PDE5, sildenafil increases cGMP levels.
Increased cGMP and its Effects
Elevated cGMP leads to several beneficial effects in PAH patients. It causes vasodilation, widening blood vessels in the lungs, reducing pulmonary vascular resistance. Simultaneously, sildenafil reduces pulmonary artery pressure and improves blood flow to the lungs. This mechanism improves cardiac output and reduces the workload on the right ventricle, a common complication of PAH.
Additional Effects beyond Vasodilation
Beyond vasodilation, sildenafil also exhibits anti-proliferative effects, hindering the growth of vascular smooth muscle cells. This is especially important in PAH, characterized by excessive cell proliferation and remodeling within the pulmonary arteries. This dual mechanism of action–vasodilation and anti-proliferation–contributes to sildenafil’s therapeutic benefits in managing PAH symptoms and improving patient outcomes.
