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Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats
BACKGROUND: Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change. AIM: To find out direct correlations between cold stress and ED...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065187/ https://www.ncbi.nlm.nih.gov/pubmed/37007851 http://dx.doi.org/10.1093/sexmed/qfac004 |
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author | Ruze, Abudureyimujiang Wang, Binghua Jin, Jin Hou, Pengcheng Tuerxun, Diliyaer Amuti, Siyiti |
author_facet | Ruze, Abudureyimujiang Wang, Binghua Jin, Jin Hou, Pengcheng Tuerxun, Diliyaer Amuti, Siyiti |
author_sort | Ruze, Abudureyimujiang |
collection | PubMed |
description | BACKGROUND: Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change. AIM: To find out direct correlations between cold stress and ED, through which to further investigate the functional roles of B1R in erectile tissue and to elucidate the therapeutic roles of the B1R antagonist in a cold stress–induced ED rat model. METHODS: Cold stress rat models are established through long-term intermittent exposure to low temperature. After their erectile function was assessed, ED rats were treated with the B1R antagonist through intraperitoneal injection. Penile tissues were obtained at the end of the experiment after measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP); the location and distribution of cytokine expression were determined by immunohistochemistry; cytokine levels and NOS and CD31 expression were detected by Western blotting; and collagen fibers and smooth muscles were observed through Masson staining. OUTCOMES: Cold stress impairs erectile function, and the B1R antagonist protects against it. RESULTS: We observed decreased erection frequency, prolonged erection latency time, decreased ICP/MAP, overexpression of B1R, increased expression of cytokines on cavernous sinus endothelium, and increased levels of collagen fibers/smooth muscles on erectile tissue in response to cold stress. Also, NOS and CD31 expression was downregulated. B1R antagonist treatment shows enhanced erectile function through increased erection frequency, shortened erection latency time, and increased ICP/MAP. Also, it reduces collagen fibers/smooth muscles, TNF-α, TGF-β1, and IL-6 and upregulates the expression of nNOS and CD31. CLINICAL TRANSLATION: Our findings cast new light on the correlations between cold stress and erectile function and potential new applications of existing B1R antagonist drugs in the field of ED. STRENGTHS AND LIMITATIONS: Our data support that cold stress impairs erectile function. B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it, and B1R inhibition protects against fibrosis and endothelial damage. Other ways of B1R antagonist blocking methods in different types of ED still need to be investigated. CONCLUSION: Long-term intermittent cold stress impairs erectile function, and B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it. B1R inhibition also protects against fibrosis and endothelial damage. Our data support the hypothesis that cold stress impairs erectile function and that B1R blockade ameliorates the symptoms of ED, possibly by reversing fibrosis and endothelial damage in erectile tissue. |
format | Online Article Text |
id | pubmed-10065187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100651872023-04-01 Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats Ruze, Abudureyimujiang Wang, Binghua Jin, Jin Hou, Pengcheng Tuerxun, Diliyaer Amuti, Siyiti Sex Med Basic Science BACKGROUND: Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change. AIM: To find out direct correlations between cold stress and ED, through which to further investigate the functional roles of B1R in erectile tissue and to elucidate the therapeutic roles of the B1R antagonist in a cold stress–induced ED rat model. METHODS: Cold stress rat models are established through long-term intermittent exposure to low temperature. After their erectile function was assessed, ED rats were treated with the B1R antagonist through intraperitoneal injection. Penile tissues were obtained at the end of the experiment after measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP); the location and distribution of cytokine expression were determined by immunohistochemistry; cytokine levels and NOS and CD31 expression were detected by Western blotting; and collagen fibers and smooth muscles were observed through Masson staining. OUTCOMES: Cold stress impairs erectile function, and the B1R antagonist protects against it. RESULTS: We observed decreased erection frequency, prolonged erection latency time, decreased ICP/MAP, overexpression of B1R, increased expression of cytokines on cavernous sinus endothelium, and increased levels of collagen fibers/smooth muscles on erectile tissue in response to cold stress. Also, NOS and CD31 expression was downregulated. B1R antagonist treatment shows enhanced erectile function through increased erection frequency, shortened erection latency time, and increased ICP/MAP. Also, it reduces collagen fibers/smooth muscles, TNF-α, TGF-β1, and IL-6 and upregulates the expression of nNOS and CD31. CLINICAL TRANSLATION: Our findings cast new light on the correlations between cold stress and erectile function and potential new applications of existing B1R antagonist drugs in the field of ED. STRENGTHS AND LIMITATIONS: Our data support that cold stress impairs erectile function. B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it, and B1R inhibition protects against fibrosis and endothelial damage. Other ways of B1R antagonist blocking methods in different types of ED still need to be investigated. CONCLUSION: Long-term intermittent cold stress impairs erectile function, and B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it. B1R inhibition also protects against fibrosis and endothelial damage. Our data support the hypothesis that cold stress impairs erectile function and that B1R blockade ameliorates the symptoms of ED, possibly by reversing fibrosis and endothelial damage in erectile tissue. Oxford University Press 2023-01-12 /pmc/articles/PMC10065187/ /pubmed/37007851 http://dx.doi.org/10.1093/sexmed/qfac004 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Basic Science Ruze, Abudureyimujiang Wang, Binghua Jin, Jin Hou, Pengcheng Tuerxun, Diliyaer Amuti, Siyiti Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title | Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title_full | Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title_fullStr | Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title_full_unstemmed | Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title_short | Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
title_sort | bradykinin b1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065187/ https://www.ncbi.nlm.nih.gov/pubmed/37007851 http://dx.doi.org/10.1093/sexmed/qfac004 |
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