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.

MATERIALS AND 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: C-S Lin, H-C Ho, K-C Chen, G Lin, L Nunes, T F Lue
• Journal: BJU international (BJU Int) Vol. 89 Issue 9 Pg. 955-60 (Jun 2002) ISSN: 1464-4096 [Print] England
• PMID: 12010247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Endothelial Growth Factors
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• NOSIP protein, human
• Ubiquitin-Protein Ligases

Topics

• Animals
• Carrier Proteins (genetics, metabolism)
• Endothelial Growth Factors (administration & dosage, pharmacology)
• Immunohistochemistry (methods)
• Impotence, Vasculogenic (enzymology)
• Injections
• Male
• Nitric Oxide Synthase (genetics, metabolism)
• Nitric Oxide Synthase Type II
• Penis (drug effects)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Ubiquitin-Protein Ligases
• Vascular Endothelial Growth Factor A