Nitric oxide (NO) is synthesised from L-arginine by endothelial nitric oxide synthase (eNOS). Its mechanism of vasodilation involves:

• A Direct binding to smooth muscle Ca2+ channels causing hyperpolarisation
• B Activation of soluble guanylyl cyclase → increased cGMP → PKG activation → Ca2+ extrusion and MLC phosphatase activation → smooth muscle relaxation ✓
• C Inhibition of thromboxane A2 receptors preventing vasoconstriction
• D Increase in cAMP via Gs-coupled receptor on smooth muscle

Explanation

Endothelial NO diffuses to adjacent vascular smooth muscle and directly activates soluble guanylyl cyclase (sGC), which converts GTP to cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), which phosphorylates multiple targets: (1) MLCP (myosin light chain phosphatase) activation removes phosphate from MLC, (2) Ca2+-ATPase activation extrudes Ca2+, and (3) K+ channel activation hyperpolarizes the cell. The net result is smooth muscle relaxation and vasodilation. This pathway is targeted by drugs like sildenafil (PDE5 inhibitor) which prevents cGMP breakdown.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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