Molecular Profile of Priapism Associated with Low Nitric Oxide Bioavailability

Abstract

<p class="first" id="P1">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 dysregulated molecular targets and signaling pathways in penile tissue of a mouse model of low NO bioavailability that have potential relevance to priapism. Neuronal + 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 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. 1279 total proteins were identified and quantified by spectral counting, 46 of which were downregulated and 110 of which were upregulated in NOS1/3 ^−/− vs. WT (P&lt;0.05). Ingenuity Pathway Analysis of differentially expressed proteins revealed increased protein kinase A and G-protein coupled receptor signaling in NOS1/3 ^−/− penis which represent potential mechanisms contributing to priapism secondary to low NO bioavailability. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/7358ed1e-c831-4b8c-8838-68a9404c444e/PubMedCentral/image/nihms-975416-f0001.jpg"/> </div> </p>