title: Adrenomedullin and angiopoietin-1 additively restore erectile function in diabetic rats: comparison with the combination therapy of vascular endothelial growth factor and angiopoietin-1.
abstract: BACKGROUND
  Erectile dysfunction (ED) is a major health problem. We have shown that adrenomedullin (AM) restores erectile function in diabetic rats.
  
  
  OBJECTIVE
  The aim of this study is to explore a better treatment for ED, we examined whether combination of AM and angiopoietin-1 (Ang-1) was more effective to treat ED than treatment with AM alone or Ang-1 alone. We also compared the effect of the combination therapy with that of treatment with vascular endothelial growth factor-A (VEGF-A).
  
  
  METHODS
  Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Adenoviruses expressing AM (AdAM), Ang-1 (AdAng-1), and VEGF-A (AdVEGF-A) were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology, and protein expression were analyzed 4 weeks after the injection of the adenoviruses.
  
  
  METHODS
  Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of α-smooth muscle actin (SMA), VE-cadherin and type I collagen was assessed by Western blot analysis.
  
  
  RESULTS
  Infection with AdAM plus AdAng-1 more effectively restored erectile function than infection with AdAM alone or AdAng-1 alone. This combination therapy restored erectile function to a level similar to that observed in the age-matched Wistar rats. Expression of SMA and VE-cadherin increased more significantly in the AdAM plus AdAng-1-treated group than in the AdAM- or AdAng-1-treated group. Although AdVEGF-A infection restored erectile function significantly, it also caused enlargement of the trabeculae of the cavernous body, aberrant angiogenesis, and overproduction of type I collagen.
  
  
  CONCLUSIONS
  These results suggested that combination therapy with AM and Ang-1 potently restored erectile function and normal morphology of the cavernous body compared with VEGF-A administration. This combination therapy will be useful to treat ED patients with a severely damaged cavernous body.
authors: The Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors: Hiroaki
authors: H
authors: Nishimatsu
authors: Etsu
authors: E
authors: Suzuki
authors: Akira
authors: A
authors: Nomiya
authors: Aya
authors: A
authors: Niimi
authors: Motofumi
authors: M
authors: Suzuki
authors: Tetsuya
authors: T
authors: Fujimura
authors: Hiroshi
authors: H
authors: Fukuhara
authors: Yukio
authors: Y
authors: Homma
mesh_terms: D053607:Adrenomedullin / Q000627:therapeutic use*; D042683:Angiopoietin-1 / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*; D000099152:Cadherin 5
chemical_list: D053607:Adrenomedullin; D042683:Angiopoietin-1; D015703:Antigens, CD; D015820:Cadherins; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5
keywords: Adrenomedullin; Angiopoietin-1; Diabetes And Erectile Function; Erectile Dysfunction; Vascular Endothelial Growth Factor