Effects of an alpha-1d adrenoreceptor antagonist (naftopidil) on bladder dysfunction after radiotherapy in female rats
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ORIGINAL ARTICLE
Effects of an alpha-1d adrenoreceptor antagonist (naftopidil) on bladder dysfunction after radiotherapy in female rats Sung Jong Lee 1,2
&
Hee Youn Kim 3 & Dong Sup Lee 3
Received: 30 April 2020 / Accepted: 23 July 2020 # The International Urogynecological Association 2020
Abstract Purpose Storage-phase bladder dysfunction can develop after pelvic radiotherapy. As the alpha-1d adrenoreceptor (a1d-AR) is dominant in the human detrusor, we aimed to investigate the effect of an a1d-AR antagonist on bladder dysfunction after pelvic radiotherapy in a rat model. Materials and methods Twenty-four female Wistar rats were used. Eight rats (14–15 weeks, 250–300 g) were randomized to three groups (normal reference group, radiation alone group and radiation plus naftopidil group). An 18-Gy dose of radiotherapy was applied to the radiation alone and radiation plus naftopidil groups. Naftopidil (20 mg/kg) was administered daily to the radiation plus naftopidil group. Four weeks after radiation, all rats underwent cystometry and were killed for reverse transcription polymerase chain reaction to detect mRNAs [a1d-AR, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF)], Western blot to detect proteins (a1d-AR, extracellular-signal-regulated kinase, BDNF and VEGF) and immunohistochemistry. Results Compared to the radiation alone group, (1) the decrease in the mRNA and protein expression of a1d-AR and VEGF was ameliorated, (2) the increase in the expression of BDNF mRNA and proteins such as extracellular-signal-regulated kinase and BDNF was suppressed, (3) submucosal thickness and vascularity on immunohistochemistry were improved, and (4) the baseline intravesical pressure and intercontraction interval in cystometry were ameliorated in the radiation plus naftopidil group. Conclusion Administration of an a1d-AR antagonist could improve storage-phase bladder dysfunction after radiotherapy not only by upregulating a1d-AR, which might decrease bladder compliance, but also by enhancing vascularity, which might protect the urinary bladder from chronic ischemic inflammation. Keywords Naftopidil . Radiotherapy . Urinary bladder
Introduction Radiation treatment of gynecological cancers can deteriorate storage-phase bladder function [1]. In brief, radiation causes Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00192-020-04472-5) contains supplementary material, which is available to authorized users. * Dong Sup Lee [email protected] 1
Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
2
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea
3
Department of Urology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93, Jungbu-daero, Paldal-gu, Suwon-si, Gyeonggi-do 16247, Republic of Korea
endarteritis, which eventually causes chronic tissue ischemia, called tissue oxid
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