Endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), activates which enzyme and by what specific biochemical mechanism to cause vascular smooth muscle relaxation?

• A Adenylyl cyclase → increases cAMP → activates PKA → inactivates RhoA kinase pathway
• B Phospholipase C → IP3 → depletes ER Ca²⁺ stores, causing relaxation by store-operated Ca²⁺ entry shutdown
• C Soluble guanylyl cyclase (sGC) → increases cGMP → activates PKG → phosphorylates MLCK and MLC phosphatase, reducing myosin light chain phosphorylation; also opens BKCa channels causing hyperpolarization ✓
• D eNOS in smooth muscle cells autogenerates NO that acts on L-type Ca²⁺ channels directly

Explanation

NO produced by eNOS in endothelium (stimulated by shear stress, acetylcholine, bradykinin via Ca²⁺-calmodulin) diffuses into adjacent vascular smooth muscle where it binds the heme group of soluble guanylyl cyclase (sGC), activating it to produce cGMP from GTP. cGMP activates protein kinase G (PKG/cGK), which phosphorylates: (1) myosin light chain kinase (MLCK) — reducing its activity; (2) large conductance Ca²⁺-activated K⁺ channels (BKCa) — causing hyperpolarization and reduced Ca²⁺ entry; (3) IP3 receptors and SERCA pumps — reducing cytosolic Ca²⁺. The net result is dephosphorylation of myosin light chains and smooth muscle relaxation. This is the mechanism of nitrate vasodilators and sildenafil (PDE5 inhibitor, which prevents cGMP degradation).

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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