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The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System

BACKGROUND: In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the...

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Autores principales: Zhang, Na, Huo, Yanan, Yao, Chen, Sun, Jie, Zhang, Yafeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213206/
https://www.ncbi.nlm.nih.gov/pubmed/35814865
http://dx.doi.org/10.1155/2022/9067167
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author Zhang, Na
Huo, Yanan
Yao, Chen
Sun, Jie
Zhang, Yafeng
author_facet Zhang, Na
Huo, Yanan
Yao, Chen
Sun, Jie
Zhang, Yafeng
author_sort Zhang, Na
collection PubMed
description BACKGROUND: In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. METHODS: Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. RESULTS: Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats (P < 0.05). After castration, captopril decreased serum Ang II concentration (P < 0.05); in female rats, icatibant increased serum Ang II concentration (P < 0.05). Captopril increased serum bradykinin concentration (P < 0.05); in male rats, icatibant decreased serum bradykinin concentration (P < 0.05). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration (P < 0.05). Icatibant decreased urine DPD/Cr in male rats (P < 0.05) and increased osteocalcin concentration in female rats (P < 0.05). Captopril increased cancellous BMD in castrated hypertensive rats (P < 0.05), and icatibant further increased cancellous BMD (P < 0.05), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength (P < 0.05), and icatibant further improved it (P < 0.05). CONCLUSION: ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.
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spelling pubmed-92132062022-07-08 The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System Zhang, Na Huo, Yanan Yao, Chen Sun, Jie Zhang, Yafeng J Renin Angiotensin Aldosterone Syst Research Article BACKGROUND: In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. METHODS: Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. RESULTS: Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats (P < 0.05). After castration, captopril decreased serum Ang II concentration (P < 0.05); in female rats, icatibant increased serum Ang II concentration (P < 0.05). Captopril increased serum bradykinin concentration (P < 0.05); in male rats, icatibant decreased serum bradykinin concentration (P < 0.05). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration (P < 0.05). Icatibant decreased urine DPD/Cr in male rats (P < 0.05) and increased osteocalcin concentration in female rats (P < 0.05). Captopril increased cancellous BMD in castrated hypertensive rats (P < 0.05), and icatibant further increased cancellous BMD (P < 0.05), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength (P < 0.05), and icatibant further improved it (P < 0.05). CONCLUSION: ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration. Hindawi 2022-06-14 /pmc/articles/PMC9213206/ /pubmed/35814865 http://dx.doi.org/10.1155/2022/9067167 Text en Copyright © 2022 Na Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Na
Huo, Yanan
Yao, Chen
Sun, Jie
Zhang, Yafeng
The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title_full The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title_fullStr The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title_full_unstemmed The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title_short The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
title_sort effect of the angiotensin-converting enzyme inhibitor on bone health in castrated hypertensive rats is mediated via the kinin-kallikrein system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213206/
https://www.ncbi.nlm.nih.gov/pubmed/35814865
http://dx.doi.org/10.1155/2022/9067167
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