Category: signaling
Nitric oxide → sGC → cGMP → PKG smooth-muscle relaxation cascade is the molecular basis of erection (cavernosal sinusoid filling) + pulmonary vasodilation (PAH treatment) + selected antiplatelet activity. PDE5 (phosphodiesterase type 5) is the cGMP-hydrolyzing enzyme concentrated in corpus cavernosum + pulmonary vascular smooth muscle. PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) preserve cGMP → potentiated NO-dependent vasodilation; nitric oxide is the obligate upstream signal (no NO, no PDE5-i benefit). Riociguat is a sGC stimulator that works NO-independently — synergistic with low endogenous NO. Critical safety: ANY PDE5 inhibitor + organic nitrate is contraindicated (life-threatening hypotension). PDE5 inhibitors also have hearing-loss + NAION (non-arteritic anterior ischemic optic neuropathy) signals. Cross-link: vasodilator_no_endothelin (NO + endothelin antagonists) + nitric_oxide_synthesis (upstream NO production).