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Alterations in angiogenic growth factors and neuronal nitric oxide synthase expression in chronic cavernosal ischemia

International Journal of Impotence Research volume 16, pages 403–411 (2004)Cite this article

Abstract

Our aim was to study anatomical and molecular changes at varying time points after the induction of cavernosal ischemia (CI) in a rabbit model of arteriogenic erectile dysfunction. Tissue structure and the expression of angiogenic and neurogenic genes were examined using immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) analyses. We found a progressive increase of erectile connective tissue together with a decrease in smooth muscle cell content as the duration of CI increased. Immunohistochemical staining showed an increase in vascular endothelial growth factor (VEGF) levels at the early stages and a decrease at the later stages of ischemia. RT-PCR analysis of VEGF and neuronal nitric oxide synthase (nNOS) confirmed these results and showed nearly a two-fold increase in VEGF and nNOS mRNA levels in the early stages of CI with a decrease at the later stages of CI. On the other hand, mRNA levels of VEGF receptor, KDR, decreased approximately by 50% over the course of CI. Our studies showed that the cellular and molecular responses of the erectile tissue to short-term ischemia are different than those seen after long-term ischemia. The dramatic reduction in KDR expression suggests that the cavernosal endothelium is very sensitive to ischemia. The similar changes in VEGF and nNOS expression over the course of CI suggest a tissue-defensive mechanism to CI via the VEGF and NO pathways. Taken together, this study suggests that supplementation of VEGF at earlier stages of ischemia may restore the damaged endothelial cells of the corpus cavernosum and support tissue perfusion.

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Author notes

  1. S Soker & A Atala

    Present address: Wake Forest University School of Medicine, Institute for Regenerative Medicine, NRC Building, 1st Floor, Medical Center Blvd., Winston-Salem, NC 27157, USA

  2. T Wang and S Soker: Both authors have contributed equally.

Authors and Affiliations

  1. Urology Department Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    T Wang, S Soker & A Atala

  2. Urology Department, Boston VA Medical Center, Boston, Massachusetts, USA

    M B Siroky

  3. Urology Department, Boston University Medical School, Boston, Massachusetts, USA

    K M Azadzoi

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  1. T Wang
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  2. S Soker
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  4. M B Siroky
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  5. K M Azadzoi
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Corresponding author

Correspondence to S Soker.

Additional information

Supported by: Veterans Affairs Central Office and NIH NIA/AG17165.

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Wang, T., Soker, S., Atala, A. et al. Alterations in angiogenic growth factors and neuronal nitric oxide synthase expression in chronic cavernosal ischemia. Int J Impot Res 16, 403–411 (2004). https://doi.org/10.1038/sj.ijir.3901186

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