Low Intensity Extracorporeal Shockwave Therapy (Li-ESWT) Improves Erectile Function in a model of Type II Diabetes Independently of NO/cGMP Pathway

PURPOSE - Erectile dysfunction (ED) is highly prevalent in type II diabetes mellitus (T2DM). Li-ESWT improves erectile function in patients with ED from vasculogenic origin including diabetes, although its mode of action remains unknown.

The effects of Li-ESWT on ED in a T2DM model compared or combined to sildenafil were investigated the hypothesis of a mode of action targeting the cavernosal NO/cGMP pathway tested.

MATERIALS AND METHODS - Goto-Kakizaki (GK), a validated model of T2DM, and age-matched Wistar rats were treated by Li-ESWT twice weekly for 3 weeks, repeated after a 3-week no-treatment interval. The rat penis was stretched and dipped into a specifically designed water-filled cage. Shockwaves were delivered by a calibrated probe yielding a controlled energy flux density (0.09mJ/mm(2)) attached to an electrohydraulic unit with a focused shockwave source allowing an accurate extrapolation to humans. Following a 4-week wash-out period, erectile function, endothelium-dependent, -independent and nitrergic relaxations of corpus cavernosum of GK rats were assessed.

RESULTS - Li-ESWT significantly improved erectile function in GK rats to the same extent as sildenafil. Li-ESWT's effects were potentiated when combined with sildenafil. Li-ESWT's effects were not associated to improved cavernosal endothelium-dependent, -independent or nitrergic reactivity.

CONCLUSIONS - Li-ESWT improves erectile function in GK rats. Unexpectedly, this was not mediated by a NO/cGMP-dependent mechanism. Sildenafil increases Li-ESWT's efficacy. This preclinical paradigm for delivering Li-ESWT to the rat's penis should help further exploration of Li-ESWT mode of action on the erectile tissue.

The Journal of urology. 2016 Mar 30 [Epub ahead of print]

Rana Assaly-Kaddoum, François Giuliano, Miguel Laurin, Diane Gorny, Micheline Kergoat, Jacques Bernabé, Yoram Vardi, Laurent Alexandre, Delphine Behr-Roussel

Pelvipharm, Montigny-le-Bretonneux, France; UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France., UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France; AP-HP, Neuro-Uro-Andrology, Dept. of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France. Pelvipharm, Montigny-le-Bretonneux, France; UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France., Pelvipharm, Montigny-le-Bretonneux, France; UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France., Metabrain Research, Chilly-Mazarin, France., Pelvipharm, Montigny-le-Bretonneux, France; UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France., Rambam Health Care Center, Haifa, Israel., Pelvipharm, Montigny-le-Bretonneux, France., Pelvipharm, Montigny-le-Bretonneux, France; UMR1179, Université Versailles Saint Quentin en Yvelines, Montigny-le-Bretonneux, France.