title: Intracavernosal injection of vascular endothelial growth factor induces nitric oxide synthase isoforms.
abstract: OBJECTIVE
  To identify genes that are affected by vascular endothelial growth factor (VEGF), as an intracavernosal injection with VEGF improved the recovery of erectile function in a rat model of arteriogenic impotence, specifically examining the three nitric oxide synthase (NOS) genes, nNOS, eNOS, and iNOS.
  
  
  METHODS
  Male rats had their pudendal arteries ligated or underwent a sham operation. They were then treated by an intracavernosal injection with 4 microg of VEGF in phosphate-buffered saline (PBS) or PBS alone. At 6 and 24 h after treatment electrostimulation was applied to the cavernosal nerve and the intracorporal pressure measured. The erectile tissue was then harvested for RNA isolation and cryo-sectioning. The isolated RNA was used for microarray and reverse transcription-polymerase chain reaction (RT-PCR) analyses, and the tissue sections for immunohistochemical analysis.
  
  
  RESULTS
  Microarray analysis detected nNOS, eNOS and iNOS at very low expression levels in PBS-treated rats; expression levels were higher for eNOS and iNOS in all VEGF-treated rats. These results were further confirmed by RT-PCR analysis. Immunohistochemical analysis identified the cavernosal endothelium and smooth muscle as the tissue types where eNOS and iNOS were up-regulated, respectively.
  
  
  CONCLUSIONS
  This is the first report of the induction of both eNOS and iNOS in the penis after intracavernosal VEGF. These events may help support a significant recovery of erectile function after interrupting the blood supply to the penis.
authors: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143, USA. clin@urol.ucsf.edu
authors: C-S
authors: CS
authors: Lin
authors: H-C
authors: HC
authors: Ho
authors: K-C
authors: KC
authors: Chen
authors: G
authors: G
authors: Lin
authors: L
authors: L
authors: Nunes
authors: T F
authors: TF
authors: Lue
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D018783:Impotence, Vasculogenic / Q000201:enzymology; D007267:Injections; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010413:Penis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases; D042461:Vascular Endothelial Growth Factor A
chemical_list: D002352:Carrier Proteins; D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C419706:NOSIP protein, human; D044767:Ubiquitin-Protein Ligases