Phosphodiesterase type 5 (PDE5)

Phosphodiesterase type 5 (PDE5) is an enzyme that hydrolyzes cyclic guanosine monophosphate (cGMP) to its inactive form, regulating intracellular cGMP levels. It is highly expressed in vascular smooth muscle and plays a key role in smooth muscle relaxation. Inhibition of PDE5 leads to increased cGMP levels, activating protein kinase G (PKG), and promoting vasodilation. PDE5 inhibitors are used to treat erectile dysfunction and pulmonary arterial hypertension, and are being explored for other cardiovascular conditions. Common side effects from pharmacological inhibition include headache, flushing, lightheadedness due to hypotension. Drug-drug interactions can occur—especially with nitrates or certain antihypertensives—requiring careful management.

Inhibition of PDE5 increases cGMP levels, which activates protein kinase G (PKG), resulting in vasodilation and enhanced blood flow.