Sildenafil acts by inhibiting –
**Core Concept**
Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor, which plays a crucial role in the management of erectile dysfunction. The underlying principle is the inhibition of PDE5 enzyme, leading to increased levels of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum.
**Why the Correct Answer is Right**
Sildenafil acts by competitively inhibiting the PDE5 enzyme, which breaks down cGMP in the corpus cavernosum. This leads to increased levels of cGMP, resulting in smooth muscle relaxation and increased blood flow to the penis. The increased cGMP levels are due to the activation of guanylyl cyclase by nitric oxide, which is released from non-adrenergic, non-cholinergic neurons. The increased blood flow and smooth muscle relaxation result in penile erection.
**Why Each Wrong Option is Incorrect**
**Option A:** Sildenafil does not act by inhibiting nitric oxide synthase, as this enzyme is involved in the production of nitric oxide, not its breakdown.
**Option B:** Sildenafil does not act by inhibiting adenylyl cyclase, as this enzyme is involved in the production of cyclic adenosine monophosphate (cAMP), not cGMP.
**Option C:** Sildenafil does not act by inhibiting phosphodiesterase type 1 (PDE1), as this enzyme is involved in the breakdown of cGMP in smooth muscle cells, but not in the corpus cavernosum.
**Clinical Pearl / High-Yield Fact**
PDE5 inhibitors are not only used for erectile dysfunction but also for pulmonary arterial hypertension, as they help to reduce pulmonary vascular resistance by increasing cGMP levels.
**Correct Answer: D. Phosphodiesterase type 5 (PDE5)**