Atrial natriuretic peptide (ANP) is released when atrial transmural pressure rises. Which intracellular mediator explains its vascular smooth muscle relaxant effect?

• A Increased cAMP via adenylate cyclase
• B Opening of voltage gated calcium channels
• C Inhibition of myosin light chain kinase by calcium calmodulin
• D Increased cGMP via particulate guanylyl cyclase ✓

Explanation

ANP binds natriuretic peptide receptor A, which is a membrane receptor with intrinsic guanylyl cyclase activity. This raises intracellular cGMP, activating protein kinase G, reducing cytosolic calcium and relaxing vascular smooth muscle, so ANP is both a vasodilator and a natriuretic agent. The nitric oxide pathway also uses cGMP but through soluble guanylyl cyclase stimulated by NO diffusion, not through a receptor enzyme. Increased cAMP mediates beta adrenergic and prostacyclin vasodilation instead.

Reference: Ganong's Review of Medical Physiology, 26th ed.

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