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J Sex Med. Author manuscript; available in PMC 2016 September 07. Published in final edited form as: J Sex Med. 2015 September ; 12(9): 1878–1885. doi:10.1111/jsm.12976.
Sub-acute hemolysis in sickle cell mice causes priapism secondary to NO imbalance and PDE5 dysregulation Nikolai A. Sopko, MD, PhD1, Hotaka Matsui, MD1, Johanna L. Hannan, PhD1, Dan Berkowitz, MD2, Hunter C. Champion, MD, PhD3, Lewis L. Hsu, MD4, Biljana Musicki, PhD1, Arthur L. Burnett, MD1, and Trinity J. Bivalacqua, MD, PhD1 1The
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James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD
2Department
of Anesthesiology and Critical Care Medicine, and Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA
3Department
of Medicine, Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore,
MD USA 4Department
of Pediatrics, University of Illinois, Chicago, IL, USA
Abstract
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Introduction—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 5 (PDE5) activities by excessive levels of reactive oxygen species (ROS) released during hemolysis. It is unknown if sub-acute 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 sub-acute setting. Aims—To investigate the effects of sub-acute hemolysis (3 month exposure) on priapism and NO pathway regulation. Methods—Mice underwent bone marrow transplantation with either SCD (BM-SS) or wild type (WT) bone marrow. BM-SS mice were treated with sildenafil 100mg/kg/day. We measured intracavernous pressure (ICP) measurements with or without cavernosal nerve stimulation (CNS) following bone marrow transplantation to assess for priapism.
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Main Outcome Measures—ICP and frequency of erections were assessed. Penile tissues were analyzed for NOS, PKG, PDE5, and ROS activities. Results—BM-SS mice demonstrated a priapism phenotype. PDE5I treatment reduced the frequency of erections in BM-SS mice (1.7 ± 1.1 vs. 5.5 ± 2.8 erections/hour, p