Molecular Profile of Priapism Associated with Low Nitric Oxide Bioavailability

Priapism
is a disorder in which prolonged penile erection persists
uncontrollably, potentially leading to tissue damage. Priapism commonly
afflicts patient populations with severely low nitric oxide (NO) bioavailability.
Because NO is a primary mediator of erection, the molecular mechanisms
involved in priapism pathophysiology associated with low NO bioavailability
are not well-understood. The objective of this study was to identify
dysregulated molecular targets and signaling pathways in penile tissue
of a mouse model of low NO bioavailability that have potential relevance
to priapism. Neuronal plus endothelial NO synthase double knockout
mice (NOS1/3–/–) were used as a model of
low NO bioavailability. Priapic-like activity was demonstrated in
the NOS1/3–/– mice relative to wild-type
(WT) mice by the measurement of prolonged erections following cessation
of electrical stimulation of the cavernous nerve. Penile tissue was
processed and analyzed by reverse-phase liquid chromatography tandem
mass spectrometry. As a result, 1279 total proteins were identified
and quantified by spectral counting, 46 of which were down-regulated
and 110 of which were up-regulated in NOS1/3–/– versus WT (P < 0.05). Ingenuity Pathway Analysis
of differentially expressed proteins revealed increased protein kinase
A and G-protein coupled receptor signaling in NOS1/3–/– penises, which represent potential mechanisms contributing to priapism
for secondary to low NO bioavailability.