Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is the primary mediator of flow-mediated vasodilation. Which of the following correctly describes its mechanism of action on vascular smooth muscle?

• A NO binds beta-adrenoceptors on smooth muscle, blocking NE-mediated vasoconstriction
• B NO activates adenylyl cyclase → cAMP → PKA → vasodilation identical to prostacyclin mechanism
• C NO directly opens L-type Ca²⁺ channels causing Ca²⁺ efflux via reverse mode operation
• D NO activates soluble guanylyl cyclase → cGMP → protein kinase G (PKG) → phosphorylates MLCK reducing its activity + opens K+ channels causing hyperpolarization → reduces Ca²⁺ → vasodilation ✓

Explanation

Endothelial eNOS (activated by shear stress via Ca²⁺/calmodulin) synthesizes NO from L-arginine. NO diffuses to adjacent VSMC and activates soluble guanylyl cyclase (sGC) → converts GTP to cGMP → activates protein kinase G (PKG). PKG: (1) phosphorylates and inhibits myosin light chain kinase (MLCK), reducing myosin phosphorylation; (2) phosphorylates phospholamban → activates SERCA → lowers cytosolic Ca²⁺; (3) activates K+ channels (BKCa) → membrane hyperpolarization → closes voltage-gated Ca²⁺ channels. Net effect: profound vasodilation. This is the mechanism exploited by nitrate drugs (glyceryl trinitrate → NO). cAMP is the prostacyclin pathway, separate from NO/cGMP.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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