These agents increase intracellular cGMP, which causes vasodilation, diuresis, natriuresis, and other beneficial renal and cardiac effects. PDE5 degrades cGMP, thus abolishing the beneficial effects of natriuretic peptides and other substances that act via NO generation, such as bradykinin and acetycholine. PDE5 inhibitors, protect against cGMP degradation by PDE5, thus augmenting the beneficial actions of natriuretic peptides, bradykinin, and acetylcholine. ANP: Atrial Natriuretic Peptide; BNP: Brain Natriuretic Peptide; B2: Bradykinin Receptor Type 2; cGMP: Cyclic Guanosine Monophosphate; eNOS: Endothelial Nitric Oxide Synthase; M: Muscarinic Receptor; NO: Nitric Oxide; NRPA,B: Natriuretic Peptide Receptors A,B respectively; PDE5: Phosphodiesterase 5.
