Because PDE5 is a major negative regulator of cGMP, PDE5 inhibitors such as sildenafil, currently used for treatment of erectile dysfunction 12 and pulmonary hypertension 13, have been used in conjunction with natriuretic peptides or other cGMP inducers to prevent degradation of cGMP by PDE5. Here, PDE5A is linked to pulmonary arterial hypertension.