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. As 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 novel molecular targets and signaling pathways in a mouse model of low NO bioavailability. Neuronal + endothelial NO synthase double knockout mice (NOS1/3-/-) were used as a model of low NO bioavailability. Priapic activity was demonstrated in the NOS1/3-/- mice relative to wild type (WT) mice by measurement of prolonged erections following cessation of electrical stimulation of the cavernous nerve. Penile tissue was processed and analyzed by reversed-phase liquid chromatography tandem mass spectrometry. 1353 total proteins were identified and quantified by spectral counting, 42 of which were downregulated and 113 of which were upregulated in NOS1/3-/- vs. WT (P<0.05). Ingenuity Pathway Analysis of differentially expressed proteins revealed increased protein kinase A signaling, G-protein coupled receptor signaling, and decreased adenosine catabolism in NOS1/3-/- penis all represent potential compensatory mechanisms that may play a role in priapism secondary to low NO bioavailability.