💊 PDE5 Inhibitor Vasodilation Mechanism Simulator

Sexual Stimulation & Nitric Oxide Release

Arousal signals travel down nerve fibers into penile tissue.

• NANC nerves: Trigger (non-adrenergic non-cholinergic)
• Endothelium + nerves: NO source (dual release sites)
• ~5 sec: NO half-life (extremely short-lived)
• ~100 µm: Diffusion range (reaches nearby muscle cells)

Parasympathetic activation

Sacral parasympathetic nerves fire during arousal.

Nitric oxide synthase

eNOS and nNOS convert L-arginine into nitric oxide.

NO diffuses freely across cell membranes instantly.

Guanylate Cyclase Activation & cGMP Synthesis

Nitric oxide switches on an enzyme that builds cGMP.

• Soluble GC: Target enzyme (binds NO directly)
• GTP: Substrate (converted to cGMP)
• ~200×: Activation boost (enzyme rate increase)
• 2nd messenger: cGMP role (activates PKG)

NO-GC binding

NO binds the heme group of guanylate cyclase.

cGMP accumulation

GTP is rapidly converted into cyclic GMP.

Rising cGMP is the direct trigger for relaxation.

Smooth Muscle Relaxation & Blood Inflow

cGMP relaxes cavernosal muscle, widening blood-filled spaces.

• PKG: Mediator (protein kinase G)
• ↓ intracellular Ca²⁺: Calcium effect (muscle relaxes)
• Expand: Lacunar spaces (fill with blood)
• ~8×: Flow increase (vs resting state)

Calcium lowering

PKG lowers calcium, releasing muscle tension.

Venous compression

Expanding tissue compresses outflow veins, trapping blood.

Trapped inflow sustains firmness during arousal.

PDE5 Breakdown of cGMP (Untreated)

PDE5 enzyme degrades cGMP, ending the erection naturally.

• PDE5: Enzyme (cGMP-specific phosphodiesterase)
• GMP: Product (inactive breakdown product)
• Cavernosal smooth muscle: Location (high PDE5 density)
• cGMP falls: Effect (muscle re-contracts)

Enzymatic hydrolysis

PDE5 cleaves cGMP into inactive GMP.

Muscle re-contraction

Falling cGMP lets calcium rise, muscle tightens.

Without inhibition, erections fade within minutes.

PDE5 Inhibitor Administered — Sildenafil Mechanism

Sildenafil blocks PDE5, letting cGMP stay elevated longer.

• Sildenafil: Drug (competitive PDE5 inhibitor)
• Catalytic pocket: Binding site (blocks cGMP access)
• ~30–60 min: Onset (after oral dose)
• ~4 hours: Duration (plasma half-life ~4h)

Competitive inhibition

Sildenafil occupies the site cGMP would bind.

Sustained vasodilation

Blocked PDE5 lets cGMP accumulate, muscle stays relaxed.

Erection requires stimulation; sildenafil only enables the response.