Chawla Saager Tilak, Shahan Jad, Soutipan Nolan, Sorkhi Samuel Ryan, Choi Yong Sun, Bae Woong Jin, Kim Sae Woong, Hsieh Tung-Chin, Rajasekaran Mahadevan Raj
Department of Research Service, San Diego VA Healthcare System, San Diego, CA, USA.
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
World J Mens Health. 2025 Apr;43(2):396-406. doi: 10.5534/wjmh.240032. Epub 2024 May 30.
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.
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).
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.
rESWT improved PMP, which may be mediated 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.
生理衰老与微血管功能障碍有关，包括阴茎微血管功能障碍，这可能导致与年龄相关的勃起功能障碍（ED）。低强度体外冲击波疗法（Li-ESWT）是一种治疗ED的非侵入性干预措施，但其对阴茎微血管功能的影响尚不清楚。我们的目标是：（i）评估Li-ESWT（特别是径向式ESWT[rESWT]）对衰老大鼠阴茎微血管灌注（PMP）的影响；（ii）阐明可能的机制；（iii）评估其对海绵体组织中血管生成和平滑肌生物标志物的影响。
对雄性大鼠（n = 9；15 - 18个月）进行麻醉，并在监测PMP的同时进行rESWT治疗。通过测量海绵体内注射N(G)-硝基-L-精氨酸甲酯（L-NAME，一氧化氮合酶抑制剂）后rESWT对PMP的影响，评估一氧化氮（NO）途径的参与情况。为了阐明细胞机制，另一组大鼠每周接受3次重复rESWT治疗（n = 4）或不接受治疗（n = 4），持续两周。在研究结束时对大鼠实施安乐死，并使用免疫染色、蛋白质印迹法和定量聚合酶链反应（qPCR）分析阴茎组织中的血管生成标志物（血管内皮生长因子-A [VEGF-A]、内皮型一氧化氮合酶 [eNOS]）和平滑肌含量（α-肌动蛋白）。
rESWT使PMP增加了两倍多（从68.5任意单位增至163.7 AU）。注射L-NAME使rESWT诱导的PMP反应降低了<40% - 50%（从185.3降至101.0 AU）。免疫染色显示海绵体中α-肌动蛋白、eNOS和VEGF-A增加，qPCR和蛋白质印迹结果证实了这些发现。
rESWT改善了PMP，这可能是通过增加VEGF表达介导的，VEGF表达增加会刺激NO/环磷酸鸟苷途径，从而导致PMP持续改善。rESWT设备可为与年龄相关的ED提供一种安全、非侵入性的治疗方法。
