title: Low Intensity Extracorporeal Shock Wave Therapy Improves Erectile Function in a Model of Type II Diabetes Independently of NO/cGMP Pathway.
abstract: OBJECTIVE
  Erectile dysfunction is highly prevalent in type II diabetes mellitus. Low intensity extracorporeal shock wave therapy improves erectile function in patients with erectile dysfunction of vasculogenic origin, including diabetes. However, its mode of action remains unknown. We investigated the effects of low intensity extracorporeal shock wave therapy compared to or combined with sildenafil on erectile dysfunction in a type II diabetes mellitus model. Our purpose was to test our hypothesis of a mode of action targeting the cavernous nitric oxide/cyclic guanosine monophosphate pathway.
  
  
  METHODS
  GK rats, a validated model of type II diabetes mellitus, and age matched Wistar rats were treated with low intensity extracorporeal shock wave therapy twice weekly for 3 weeks. Treatment was repeated after a 3-week no-treatment interval. The penis was stretched and dipped in a specifically designed water-filled cage. Shock waves were delivered by a calibrated probe yielding a controlled energy flux density (0.09 mJ/mm(2)). The probe was attached to an electrohydraulic unit with a focused shock wave source, allowing for accurate extrapolation to humans. Following a 4-week washout period erectile function was assessed as well as endothelium dependent and independent, and nitrergic relaxations of the corpus cavernosum of GK rats.
  
  
  RESULTS
  Low intensity extracorporeal shock wave therapy significantly improved erectile function in GK rats to the same extent as sildenafil. Treatment effects were potentiated when combined with sildenafil. Shock wave effects were not associated with improved cavernous endothelium dependent or independent, or nitrergic reactivity.
  
  
  CONCLUSIONS
  Low intensity extracorporeal shock wave therapy improved erectile function in GK rats. Unexpectedly, this was not mediated by a nitric oxide/cyclic guanosine monophosphate dependent mechanism. Sildenafil increased shock wave efficacy. This preclinical paradigm to deliver low intensity extracorporeal shock wave therapy to the rat penis should help further exploration of the mode of action of this therapy on erectile tissue.
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.
authors.forename: Rana
authors.initials: R
authors.lastname: Assaly-Kaddoum
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France; AP-HP, Neuro-Uro-Andrology, Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France. Electronic address: francois.giuliano@uvsq.fr.
authors.forename: François
authors.initials: F
authors.lastname: Giuliano
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.
authors.forename: Miguel
authors.initials: M
authors.lastname: Laurin
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Gorny
authors.affiliation: Metabrain Research, Chilly-Mazarin, France.
authors.forename: Micheline
authors.initials: M
authors.lastname: Kergoat
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernabé
authors.affiliation: Rambam Health Care Center, Haifa, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vardi
authors.affiliation: Pelvipharm, Montigny-le-Bretonneux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alexandre
authors.affiliation: UMR INSERM 1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D000074059:Extracorporeal Shockwave Therapy / Q000379:methods*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010410:Penile Erection / Q000502:physiology*; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D006152:Cyclic GMP
keywords: diabetes mellitus; erectile dysfunction; penis; sildenafil citrate; ultrasonic waves