title: Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy.
abstract: BACKGROUND
  Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to phosphodiesterase 5 inhibitors, which act downstream of cavernous nerve (CN)-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation.
  
  
  OBJECTIVE
  This study aimed to determine if topically applied NO-releasing nanoparticles (NO-NPs) could elicit erections in a rat model of RP through increased blood flow.
  
  
  METHODS
  Twenty-six Sprague Dawley rats underwent bilateral transection of the CN. One week later, NO-NPs were applied topically to the penile shaft in dimethylsulfoxide (DMSO) gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty NPs. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-NPs on blood flow was determined using a hamster dorsal window chamber.
  
  
  METHODS
  Animals were investigated for spontaneous erections, onset and duration of erectile response, and basal ICP/BP ratio. Microcirculatory blood flow was determined through measurements of arteriolar and venular diameter and red blood cell velocity.
  
  
  RESULTS
  Eight of 10 animals treated with NO-NPs suspended in DMSO gel had significant increases in basal ICP/BP, and 6 out of these 10 animals demonstrated spontaneous erections of approximately 1 minute in duration. Time to onset of spontaneous erections ranged from 5 to 37 minutes, and they occurred for at least 45 minutes. Similar results were observed with NO-NPs applied in coconut oil. No erectile response was observed in control animal models treated with empty NPs. The hamster dorsal window chamber experiment demonstrated that NO-NPs applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes.
  
  
  CONCLUSIONS
  Topically applied NO-NPs induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that NO-NPs would be useful in penile rehabilitation of patients following RP.
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Moses
authors.initials: M
authors.lastname: Tar
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Mahantesh
authors.initials: M
authors.lastname: Navati
authors.forename: Brandon
authors.initials: B
authors.lastname: Adler
authors.forename: Parimala
authors.initials: P
authors.lastname: Nacharaju
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
authors.forename: Joel
authors.initials: J
authors.lastname: Friedman
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Davies
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D011468:Prostatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058986:Phosphodiesterase 5 Inhibitors
keywords: Cavernous Nerve; Erectile Dysfunction; Microcirculation; Nanoparticle; Nitric Oxide; Radical Prostatectomy