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

Nikolai A. Sopko, Hotaka Matsui, Johanna L. Hannan, Dan E Berkowitz, Hunter C. Champion, Lewis L. Hsu, Biljana Musicki, Arthur Burnett, Trinity Bivalacqua

Research output: Contribution to journalArticle

Abstract

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 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. Aims: The aim of this study was to investigate the effects of subacute 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 cavernous nerve stimulation following bone marrow transplantation to assess for priapism. Main Outcome Measures: ICP and frequency of erections were assessed. Penile tissues were analyzed for NOS, protein kinase G (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 per hour, P

Original languageEnglish (US)
Pages (from-to)1878-1885
Number of pages8
JournalJournal of Sexual Medicine
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2015

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Type 5 Cyclic Nucleotide Phosphodiesterases
Priapism
Hemolysis
Phosphodiesterase 5 Inhibitors
Sickle Cell Anemia
Bone Marrow Transplantation
Nitric Oxide Synthase
Reactive Oxygen Species
Homeostasis
Penile Erection
Pressure
Cyclic GMP-Dependent Protein Kinases
Bone Marrow
Outcome Assessment (Health Care)
Phenotype
Therapeutics
Research

Keywords

  • Endothelial nitric oxide synthase
  • PDE5 inhibitor
  • Phosphodiesterase 5
  • Priapism
  • Reactive oxygen species
  • Sickle cell disease

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation. / Sopko, Nikolai A.; Matsui, Hotaka; Hannan, Johanna L.; Berkowitz, Dan E; Champion, Hunter C.; Hsu, Lewis L.; Musicki, Biljana; Burnett, Arthur; Bivalacqua, Trinity.

In: Journal of Sexual Medicine, Vol. 12, No. 9, 01.09.2015, p. 1878-1885.

Research output: Contribution to journalArticle

Sopko, Nikolai A. ; Matsui, Hotaka ; Hannan, Johanna L. ; Berkowitz, Dan E ; Champion, Hunter C. ; Hsu, Lewis L. ; Musicki, Biljana ; Burnett, Arthur ; Bivalacqua, Trinity. / Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation. In: Journal of Sexual Medicine. 2015 ; Vol. 12, No. 9. pp. 1878-1885.
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AU - Hannan, Johanna L.

AU - Berkowitz, Dan E

AU - Champion, Hunter C.

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