Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

New insights into the role of endothelin-1 in radiation-associated impotence

Abstract

The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 μg/30 μl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Mollenkamp JS, Cooper JF, Kagan AR. . Clinical experience with supervoltage radiotherapy in carcinoma of the prostate: a preliminary report. J Urol 1975 113, 374–377.

    Article  CAS  Google Scholar 

  2. Ray GR, Cassady JR, Bagshaw MA. . Definitive radiation therapy of carcinoma of the prostate. A report on 15 y of experience. Radiology 1973 106, 407–418.

    Article  CAS  Google Scholar 

  3. Goldstein I et al.Radiation-associated impotence: a clinical study of its mechanism. JAMA 1984 251, 903–910.

    Article  CAS  Google Scholar 

  4. Lindsay S, Kohn HI, Dakin RL, Jew J. . Aortic arteriosclerosis in the dog after localized aortic X-irradiation. Circ Res 1962 10, 51–60.

    Article  CAS  Google Scholar 

  5. Konings AW, Hardonk MJ, Wieringa RA, Lamberts HB. . Initial events in radiation-induced atheromatosis: I. Activation of lysosomal enzymes. Strahlentherapie 1975 150, 444–448.

    CAS  PubMed  Google Scholar 

  6. Carrier S et al.Radiation-induced decrease in nitric oxide synthase containing nerves in the rat penis. Radiology 1995 195, 95–99.

    Article  CAS  Google Scholar 

  7. Swanson DA. . Cancer of the bladder and prostate: the impact of therapy on sexual function. In: Von Eschenback AC, Rodriguez DB (eds). Sexual Rehabilitation of the Urologic Cancer Patient GK Hall & Co: Boston 1981 89–107.

    Google Scholar 

  8. Silverberg GD, Britt RH, Goffinet DR. . Radiation-induced carotid artery disease. Cancer 1978 41, 130–137.

    Article  CAS  Google Scholar 

  9. Nylander G, Pettersson F, Swedenborg J. . Localized arterial occlusions in patients treated with pelvic field radiation for cancer. Cancer 1978 41, 2158–2161.

    Article  CAS  Google Scholar 

  10. Shenouda G, Labateya M, Souhami L, Podgorsak EB. . Radiation-induced endothelin production by human endothelial cells in vitro. Intl J Radiat Oncol Biol Phys 1992 24, 276.

    Article  Google Scholar 

  11. Saenz de Tejada I et al.Endothelin: localization, synthesis, activity, and receptor types in human penile corpus cavernosum. Am J Physiol 1995 261, H1078–H1085.

    Google Scholar 

  12. Lerner SE, Melman A, Christ GJ. . A review of erectile dysfunction: new insights and more questions. J Urol 1993 149, 1246–1255.

    Article  CAS  Google Scholar 

  13. Christ GJ, Lerner SE, Kim DC, Melman A. . Endothelin-1 as a putative modulator of erectile dysfunction: I. Characteristics of contraction of isolated corporal tissue strips. J Urology 1995 153, 1998–2003.

    Article  CAS  Google Scholar 

  14. Zhao W, Christ GJ. . Endothelin-1 as a putative modulator of erectile dysfunction. II. Calcium mobilization in cultured human corporal smooth muscle cells. J Urology 1995 154, 1571–1579.

    Article  CAS  Google Scholar 

  15. Imai T et al.Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland. Biochem Biophys Res Commun 1992 182, 1115–1121.

    Article  CAS  Google Scholar 

  16. Resink TJ et al.Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem Biophys Res Commun 1990 168, 1303–1310.

    Article  CAS  Google Scholar 

  17. Miller WL, Redfield MM, Burnett JC. . Integrated cardiac, renal, and endocrine actions of endothelin. J Clin Invest 1989 83, 317–320.

    Article  CAS  Google Scholar 

  18. New RB, Sampson AC, Spirale FG. . Effects of combined angiotensin II and endothelin receptor blockade with developing heart failure: effects on left ventricular performance. Kidney Int 2000 58, 242–250.

    Article  Google Scholar 

  19. Ikeda T et al.Antihypertensive effects of a mixed endothelin A and B receptor antagonist in the presence of an AT-1 receptor antagonist, MK 954. J Cardiovasc Pharmacol 2000 36(Suppl 5), S337–S341.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Merlin, S., Brock, G., Begin, L. et al. New insights into the role of endothelin-1 in radiation-associated impotence. Int J Impot Res 13, 104–109 (2001). https://doi.org/10.1038/sj.ijir.3900652

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3900652

Keywords

This article is cited by

Search

Quick links