title: Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  Chronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED.
  
  
  OBJECTIVE
  We evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED.
  
  
  METHODS
  Sprague-Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM-I), DM treated with PDE5 (DM-P), and DM treated with insulin and PDE5 (DM-I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM-I group was treated with a daily injection of neutral protamine Hagedorn, and the DM-P group was treated with a daily dosage of 20 mg/kg PDE5 (DA-8159) for 4 weeks. The DM-I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed.
  
  
  METHODS
  Erectile function and histological and biochemical markers in corporal tissue.
  
  
  RESULTS
  Rats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM-I and DM-P groups showed intermediate erectile function between the DM and C groups. Rats in the DM-I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM-I = DM-P < DM-I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order.
  
  
  CONCLUSIONS
  Chronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5.
authors.affiliation: Department of Urology, Konkuk University Hospital, Seoul, Korea.
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Choi
authors.forename: Oh Seong
authors.initials: OS
authors.lastname: Kwon
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Cho
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Paick
authors.forename: Soo Woong
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013449:Sulfonamides / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D052250:Nitric Oxide Synthase Type III; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D013311:Streptozocin; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides
keywords: Animal Model of Diabetes; Diabetes Mellitus; Erectile Dysfunction