Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation

The Journal of Sexual Medicine
Nikolai A SopkoTrinity J Bivalacqua

Abstract

Recent research suggests that priapism in sickle cell disease (SCD) is due to dysregulation of penile erection homeostasis including alteration of nitric oxide synthase (NOS) and phosphodiesterase type 5 (PDE5) activities by excessive levels of reactive oxygen species (ROS) released during hemolysis. It is unknown if subacute exposure to hemolysis is sufficient or if chronic reconditioning of erectile tissues is required for perturbation of homeostatic pathways and whether PDE5 inhibitor (PDE5I) treatment can restore erectile homeostasis in the subacute setting. The aim of this study was to investigate the effects of subacute hemolysis (3-month exposure) on priapism and NO pathway regulation. Mice underwent bone marrow transplantation with either SCD (BM-SS) or wild-type (WT) bone marrow. BM-SS mice were treated with sildenafil 100 mg/kg/day. We measured intracavernous pressure (ICP) measurements with or without cavernous nerve stimulation following bone marrow transplantation to assess for priapism. ICP and frequency of erections were assessed. Penile tissues were analyzed for NOS, protein kinase G (PKG), PDE5, and ROS activities. BM-SS mice demonstrated a priapism phenotype. PDE5I treatment reduced the frequency of erections ...Continue Reading

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Citations

Jun 23, 2019·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·Michael H GreenwaldClaudia R Morris
Mar 20, 2020·Expert Opinion on Therapeutic Targets·Biljana Musicki, Arthur L Burnett
Feb 3, 2018·Journal of Proteome Research·Justin D La FavorArthur L Burnett

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