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Schematic representation of NO/PDE5/PKG pathway in smooth muscle cells.
NO released from endothelial cells activates soluble guanylate cyclase that produces cGMP from GTP. cGMP activates PKG that phosphorylates several substrates thus inhibiting smooth muscle contraction and promoting angiogenesis. PDE5 reverses this condition by hydrolizing cGMP to GMP while PDE5i (sildenafil, vardenafil, tadalafil, avanafil) all promote smooth muscle relaxation by inhibiting cGMP accumulation.
