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Inhibiting the action of phosphodiesterase 5A (PDE5A), the first member of the PDE family to be discovered, improves erectile dysfunction and pulmonary hypertension. Although PDE5A inhibition theoretically could protect against cardiovascular disease as well, results of clinical trials have been disappointing.
An international team detected a related molecule, PDE9A, in cardiac myocytes of several mammals, including humans, and showed that cardiac hypertrophy was associated with increased PDE9A levels in myocytes. The team then showed that a known inhibitor of PDE9A prevented, and even reversed, heart failure in mouse models of cardiac pressure overload (caused by experimentally constricting the aorta). Careful experiments with controls show…