Nitric oxide (NO) causes vascular smooth muscle relaxation. Which downstream mechanism mediates this vasodilation?

• A NO inhibits adenylyl cyclase → ↓cAMP → reduced PKA activity → smooth muscle relaxation
• B NO directly opens ATP-sensitive K+ channels (KATP) independent of guanylyl cyclase
• C NO activates phospholipase A2 → arachidonic acid → PGI2 → IP receptor → Gs → ↑cAMP
• D NO activates soluble guanylyl cyclase → ↑cGMP → protein kinase G → dephosphorylation of myosin light chain and activation of BKCa channels → hyperpolarization and relaxation ✓

Explanation

Endothelium-derived NO diffuses into vascular smooth muscle cells and activates soluble guanylyl cyclase (sGC), which converts GTP to cGMP. Elevated cGMP activates protein kinase G (PKG), which phosphorylates: myosin light chain phosphatase (activating it, dephosphorylating MLC → relaxation), large-conductance Ca2+-activated K+ channels (BKCa, causing hyperpolarization and reducing Ca2+ influx), and IP3 receptor-associated cGMP kinase substrate (IRAG, reducing Ca2+ release from SR). PDE5 (targeted by sildenafil) degrades cGMP and limits this pathway.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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