A patient is given an infusion of a drug that selectively increases vascular smooth muscle cAMP. Which vascular response is expected?

• A Vasoconstriction via PKA-mediated myosin light chain kinase activation
• B Vasodilation via PKA-mediated phosphorylation of myosin light chain kinase (MLCK), reducing its activity ✓
• C Initial vasodilation followed by reflex vasoconstriction via baroreceptors
• D Vasodilation via cAMP opening Ca2+-activated K+ channels

Explanation

In vascular smooth muscle, the primary contractile trigger is phosphorylation of myosin regulatory light chains (MLC) by Ca2+-calmodulin-activated MLCK. Elevated cAMP activates PKA, which phosphorylates MLCK, reducing its affinity for the Ca2+-calmodulin complex and impairing MLC phosphorylation — net effect is smooth muscle relaxation and vasodilation. Additionally, PKA phosphorylates phospholamban, increasing SERCA activity and lowering cytosolic Ca2+. This is the mechanism of beta-2 agonist vasodilation and is also relevant to PDE inhibitors (which raise cAMP). Baroreceptor reflexes would occur secondarily but are not the direct drug action.

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

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