Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction

Purpose: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascula...

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Main Authors: Saager Tilak Chawla, Jad Shahan, Nolan Soutipan, Samuel Ryan Sorkhi, Yong Sun Choi, Woong Jin Bae, Sae Woong Kim, Tung-Chin Hsieh, Mahadevan Raj Rajasekaran
Format: Article
Language:English
Published: Korean Society for Sexual Medicine and Andrology 2025-04-01
Series:The World Journal of Men's Health
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author Saager Tilak Chawla
Jad Shahan
Nolan Soutipan
Samuel Ryan Sorkhi
Yong Sun Choi
Woong Jin Bae
Sae Woong Kim
Tung-Chin Hsieh
Mahadevan Raj Rajasekaran
author_facet Saager Tilak Chawla
Jad Shahan
Nolan Soutipan
Samuel Ryan Sorkhi
Yong Sun Choi
Woong Jin Bae
Sae Woong Kim
Tung-Chin Hsieh
Mahadevan Raj Rajasekaran
author_sort Saager Tilak Chawla
collection DOAJ
description Purpose: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li- ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue. Materials and Methods: Male rats (n=9; 15–18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor- A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR). Results: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%–50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results. Conclusions: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.
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publishDate 2025-04-01
publisher Korean Society for Sexual Medicine and Andrology
record_format Article
series The World Journal of Men's Health
spelling doaj-art-4691fce3ffa741f58d1bcd75223858b62025-08-20T02:41:59ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-04-0143239640610.5534/wjmh.240032Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile DysfunctionSaager Tilak Chawla0https://orcid.org/0009-0009-3864-4251Jad Shahan1https://orcid.org/0009-0006-5408-4125Nolan Soutipan2https://orcid.org/0009-0006-1456-8707Samuel Ryan Sorkhi3https://orcid.org/0000-0002-0454-3390Yong Sun Choi4https://orcid.org/0000-0003-2903-0812Woong Jin Bae5https://orcid.org/0000-0001-7703-1161Sae Woong Kim6https://orcid.org/0000-0002-9127-9400Tung-Chin Hsieh7https://orcid.org/0000-0002-4149-7610Mahadevan Raj Rajasekaran8https://orcid.org/0000-0003-4188-1628Department of Research Service, San Diego VA Healthcare System, San Diego, CA, USADepartment of Research Service, San Diego VA Healthcare System, San Diego, CA, USADepartment of Research Service, San Diego VA Healthcare System, San Diego, CA, USADepartment of Research Service, San Diego VA Healthcare System, San Diego, CA, USADepartment of Urology, College of Medicine, The Catholic University of Korea, Seoul, KoreaDepartment of Urology, College of Medicine, The Catholic University of Korea, Seoul, KoreaDepartment of Urology, College of Medicine, The Catholic University of Korea, Seoul, KoreaDepartment of Urology, University of California, San Diego, CA, USADepartment of Research Service, San Diego VA Healthcare System, San Diego, CA, USAPurpose: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li- ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue. Materials and Methods: Male rats (n=9; 15–18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor- A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR). Results: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%–50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results. Conclusions: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.erectile dysfunctionextracorporeal shockwave therapyfibrosislaser speckle contrast imagingmicrocirculationpenis
spellingShingle Saager Tilak Chawla
Jad Shahan
Nolan Soutipan
Samuel Ryan Sorkhi
Yong Sun Choi
Woong Jin Bae
Sae Woong Kim
Tung-Chin Hsieh
Mahadevan Raj Rajasekaran
Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
The World Journal of Men's Health
erectile dysfunction
extracorporeal shockwave therapy
fibrosis
laser speckle contrast imaging
microcirculation
penis
title Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
title_full Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
title_fullStr Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
title_full_unstemmed Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
title_short Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction
title_sort radial type low intensity extracorporeal shockwave therapy enhances penile microvascular perfusion in an aging rat model a novel interventional strategy to treat erectile dysfunction
topic erectile dysfunction
extracorporeal shockwave therapy
fibrosis
laser speckle contrast imaging
microcirculation
penis
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