In particular, PDE2A is elevated in human stellectomised tissue from patients with sympathetic dysautonomia.20 PDE2A is a dual-substrate enzyme, able to hydrolyze both cAMP and cGMP with approximately equal affinity and efficacy.21 Overexpressing PDE2A in healthy sympathetic neurons recapitulates the decreased levels of cGMP17 associated with abnormal sympathetic transmission that is observed in prehypertensive rats, although its site of action in the neuron has not been established. Here, PDE2A is linked to dysautonomia.