Category: signaling
Vascular tone arises from the balance of vasoconstrictors (endothelin-1, angiotensin II, NE) and vasodilators (NO/sGC/cGMP cascade, prostacyclin, ANP/BNP). Therapeutic vasodilators split: NO donors (organic nitrates → NO → sGC activation → cGMP → PKG → vasodilation) are tolerance-prone at chronic exposure. Soluble guanylate cyclase (sGC) stimulators (riociguat) act NO-independently — synergistic with endogenous NO. PDE5 inhibitors (sildenafil family, not all in registry) preserve cGMP. Endothelin-receptor antagonists (bosentan dual ET-A/B, macitentan, ambrisentan ET-A-selective) blunt the most potent endogenous vasoconstrictor — PAH indication. Direct smooth-muscle relaxants (hydralazine, minoxidil) — mechanism less specified. ARNI (sacubitril) blocks neprilysin → preserves ANP/BNP → natriuresis + vasodilation.