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.

  • Article
  • Published:

Effects of low-intensity shock wave therapy (LiST) on the erectile tissue of naturally aged rats

Abstract

Low-intensity shock wave therapy (LiST) improves erectile function in patients with erectile dysfunction (ED), probably by promoting angiogenesis as suggested by studies on animals with comorbidities as disease associated ED models. We aim to investigate the effects of LiST on erectile tissue of healthy, naturally aged rats. Twelve naturally aged male rats were randomized into two groups: control group (n = 6) and LiST-treatment group (n = 6). Young rats (8 weeks) (n = 6) was also used as control. Each rat in treatment group received 300 shock waves with an energy flux density of 0.09 mJ/mm2 at 2 Hz. Sessions were repeated three times/week for 2 weeks, followed by a 2-week washout period. Real-time RT-PCR for the expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nerve growth factor (NGF), neuronal NOS (nNOS), as well as α1 and α2-adrenergic receptors (α1AR, α2AR) was performed, followed by immunohistochemical analysis (IHC) to evaluate protein expression. The expressions of VEGF, eNOS, and α2AR/α1AR ratio were increased after LiST (p = 0.039, p = 0.008, and p = 0.006 respectively). The increase of VEGF, eNOS, and α2AR was confirmed in IHC (p = 0.013, p = 0.092, and p = 0.096, respectively). The increase of VEGF and eNOS seem to play key role in the mechanism of action of LiST, apparently by inducing angiogenesis. The altered expression of α1/α2-adrenergic receptors could indicate a decrease in sympathetic activity. LiST showed to partially reverse changes associated with aging in erectile tissue of rats, which supports future research for ED prevention.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I. Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction. Eur Urol. 2010;58:243–8.

    Article  Google Scholar 

  2. Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of low-intensity extracorporeal shockwave therapy on erectile dysfunction: A systematic review and meta-analysis. J Sex Med. 2017;14:27–35.

    Article  Google Scholar 

  3. Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity extracorporeal shock wave treatment improves erectile function: a systematic review and meta-analysis. Eur Urol. 2017;71:223–33.

    Article  Google Scholar 

  4. Angulo JC, Arance I, de Las Heras MM, Meilán E, Esquinas C, Andrés EM. Efficacy of low-intensity shock wave therapy for erectile dysfunction: A systematic review and meta-analysis. Actas Urol Esp. 2016. Actas Urol Esp. 2017 Oct;41(8):479-90.

    Article  CAS  Google Scholar 

  5. Fu M, Sun C.-K, Lin Y.-C, Wang C.-J, Wu C.-J, Ko S.-F, et al. Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment. PLoS ONE. 2011;6:e24342.

    Article  CAS  Google Scholar 

  6. Mittermayr R, Hartinger J, Antonic V, Meinl A, Pfeifer S, Stojadinovic A, et al. Extracorporeal shock wave therapy (ESWT) minimizes ischemic tissue necrosis irrespective of application time and promotes tissue revascularization by stimulating angiogenesis. Ann Surg. 2011;253:1024–32.

    Article  Google Scholar 

  7. Goertz O, Lauer H, Hirsch T, Ring A, Lehnhardt M, Langer S, et al. Extracorporeal shock waves improve angiogenesis after full thickness burn. Burns. 2012;38:1010–8.

    Article  CAS  Google Scholar 

  8. Kisch T, Wuerfel W, Forstmeier V, Liodaki E, Stang FH, Knobloch K, et al. Repetitive shock wave therapy improves muscular microcirculation. J Surg Res. 2016;201:440–5.

    Article  Google Scholar 

  9. Chen YJ, Wurtz T, Wang CJ, Kuo YR, Yang KD, Huang HC, et al. Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats. J Orthop Res. 2004;22:526–34.

    Article  CAS  Google Scholar 

  10. Mense S, Hoheisel U. Shock wave treatment improves nerve regeneration in the rat. Muscle Nerve. 2013;47:702–10.

    Article  Google Scholar 

  11. Muller A, Akin-Olugbade Y, Deveci S, Donohue JF, Tal R, Kobylarz KA, et al. The impact of shock wave therapy at varied energy and dose levels on functional and structural changes in erectile tissue. Eur Urol. 2008;53:635–42.

    Article  Google Scholar 

  12. Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, et al. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med. 2013;10:738–46.

    Article  CAS  Google Scholar 

  13. Liu J, Zhou F, Li GY, Wang L, Li HX, Bai GY, et al. Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats. Int J Mol Sci. 2013;14:10661–73.

    Article  Google Scholar 

  14. Assaly-Kaddoum R, Giuliano F, Laurin M, Gorny D, Kergoat M, Bernabe J, et al. Low intensity extracorporeal shock wave therapy improves erectile function in a model of type II diabetes independently of NO/cGMP pathway. J Urol. 2016;196:950–6.

    Article  Google Scholar 

  15. Shan HT, Zhang HB, Chen WT, Chen FZ, Wang T, Luo JT, et al. Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats. Asian J Androl. 2017;19:26–33.

    CAS  PubMed  Google Scholar 

  16. Li H, Matheu MP, Sun F, Wang L, Sanford MT, Ning H, et al. Low-energy shock wave therapy ameliorates erectile dysfunction in a pelvic neurovascular injuries rat model. J Sex Med. 2016;13:22–32.

    Article  Google Scholar 

  17. Toda N. Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther. 2012;133:159–76.

    Article  CAS  Google Scholar 

  18. Dalaklioglu S, Sahin P, Tasatargil A, Celik-Ozenci C. Pravastatin improves the impaired nitric oxide-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in aged rats. Aging Male. 2014;17:259–66.

    Article  CAS  Google Scholar 

  19. Zlobec I, Steele R, Michel RP, Compton CC, Lugli A, Jass JR. Scoring ofp53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer. Mod Pathol. 2006;19:1236–42.

    Article  CAS  Google Scholar 

  20. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61.

    Article  CAS  Google Scholar 

  21. Jeon SH, Shrestha KR, Kim RY, Jung AR, Park YH, Kwon O, et al. Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. Urology. 2016;88:226–e1.

    Article  Google Scholar 

  22. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25:581–611.

    Article  CAS  Google Scholar 

  23. Fukumura D, Gohongi T, Kadambi A, Izumi Y, Ang J, Yun CO, et al. Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proc Natl Acad Sci USA. 2001;98:2604–9.

    Article  CAS  Google Scholar 

  24. Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, et al. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest. 1997;99:2625.

    Article  CAS  Google Scholar 

  25. Musicki B, Kramer MF, Becker RE, Burnett AL. Age‐related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med. 2005;2:347–57.

    Article  CAS  Google Scholar 

  26. Sun FY, Guo X. Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor. J Neurosci Res. 2005;79:180–4.

    Article  CAS  Google Scholar 

  27. Giuliano F, Bernabe J, Jardin A, Rousseau JP. Antierectile role of the sympathetic nervous system in rats. J Urol. 1993;150:519–24.

    Article  CAS  Google Scholar 

  28. de Tejada IS, Kim NN, Goldstein I, Traish AM. Regulation of pre-synaptic alpha adrenergic activity in the corpus cavernosum. Int J Impot Res. 2000;12(S1):S20.

    Article  Google Scholar 

  29. Silva FH, Lanaro C, Leiria LO, Rodrigues RL, Davel AP, Claudino MA, et al. Oxidative stress associated with middle aging leads to sympathetic hyperactivity and downregulation of soluble guanylyl cyclase in corpus cavernosum. Am J Physiol Heart Circ Physiol. 2014;307:H1393–400.

    Article  CAS  Google Scholar 

  30. Morrison JF, Pallot DJ, Sheen R, Dhanasekaran S, Mensah-Brown EP. The effects of age and streptozotocin diabetes on the sympathetic innervation in the rat penis. Mol Cell Biochem. 2007;295:53–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Medispec Ltd, Israel provided the device and the applicators for the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to I. Sokolakis.

Ethics declarations

Conflict of interest

D Kalyvianakis: Research grants from Medispec (Israel) and Dornier MedTech (Germany). D Hatzichristou: Research grants and speaker honoraria from Medispec (Israel), Dornier MedTech (Germany) and Menarini (Italy). The other authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sokolakis, I., Dimitriadis, F., Psalla, D. et al. Effects of low-intensity shock wave therapy (LiST) on the erectile tissue of naturally aged rats. Int J Impot Res 31, 162–169 (2019). https://doi.org/10.1038/s41443-018-0064-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-018-0064-0

This article is cited by

Search

Quick links