Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice

Abstract Occlusal disharmony is known to affect not only the oral cavity environment, but also the autonomic nervous system in the heart. Since the renin-angiotensin system (RAS) inhibitor captopril (Cap) is one of the first-line drugs for preventing cardiac remodeling in patients with heart failure...

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Main Authors: Aiko Ito, Yoshiki Ohnuki, Kenji Suita, Ichiro Matsuo, Misao Ishikawa, Takao Mitsubayashi, Yasumasa Mototani, Kenichi Kiyomoto, Michinori Tsunoda, Akinaka Morii, Megumi Nariyama, Yoshio Hayakawa, Hiroshi Tomonari, Satoshi Okumura
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-43099-6
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author Aiko Ito
Yoshiki Ohnuki
Kenji Suita
Ichiro Matsuo
Misao Ishikawa
Takao Mitsubayashi
Yasumasa Mototani
Kenichi Kiyomoto
Michinori Tsunoda
Akinaka Morii
Megumi Nariyama
Yoshio Hayakawa
Hiroshi Tomonari
Satoshi Okumura
author_facet Aiko Ito
Yoshiki Ohnuki
Kenji Suita
Ichiro Matsuo
Misao Ishikawa
Takao Mitsubayashi
Yasumasa Mototani
Kenichi Kiyomoto
Michinori Tsunoda
Akinaka Morii
Megumi Nariyama
Yoshio Hayakawa
Hiroshi Tomonari
Satoshi Okumura
author_sort Aiko Ito
collection DOAJ
description Abstract Occlusal disharmony is known to affect not only the oral cavity environment, but also the autonomic nervous system in the heart. Since the renin-angiotensin system (RAS) inhibitor captopril (Cap) is one of the first-line drugs for preventing cardiac remodeling in patients with heart failure, we hypothesized that Cap might prevent cardiac dysfunction induced by occlusal disharmony. Here, to test this idea, we used our bite-opening (BO) mouse model, which was developed by cementing a suitable appliance onto the mandibular incisor. Mice were divided into four groups: (1) Control, (2) BO, (3) Cap, and (4) BO + Cap. After 2 weeks, we evaluated cardiac function by echocardiography and confirmed that cardiac function was significantly decreased in the BO group compared to the control, while Cap ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and oxidative stress-induced myocardial damage in the BO group were significantly increased versus the control, and these increases were suppressed by Cap. Cardiac dysfunction induced by BO was associated with dual phosphorylation on PKCδ (Tyr-311/Thr-505), leading to activation of CaMKII with increased phosphorylation of RyR2 and phospholamban. Our results suggest that the RAS might play an important role in the development of cardiac diseases induced by occlusal anomalies.
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spelling doaj.art-f210d657f7984093850737c5ae96407e2023-11-20T09:19:50ZengNature PortfolioScientific Reports2045-23222023-11-0113111910.1038/s41598-023-43099-6Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in miceAiko Ito0Yoshiki Ohnuki1Kenji Suita2Ichiro Matsuo3Misao Ishikawa4Takao Mitsubayashi5Yasumasa Mototani6Kenichi Kiyomoto7Michinori Tsunoda8Akinaka Morii9Megumi Nariyama10Yoshio Hayakawa11Hiroshi Tomonari12Satoshi Okumura13Department of Orthodontics, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Periodontology, Tsurumi University School of Dental MedicineDepartment of Oral Anatomy, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Pediatric Dentistry, Tsurumi University School of Dental MedicineDepartment of Dental Anesthesiology, Tsurumi University School of Dental MedicineDepartment of Orthodontics, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineAbstract Occlusal disharmony is known to affect not only the oral cavity environment, but also the autonomic nervous system in the heart. Since the renin-angiotensin system (RAS) inhibitor captopril (Cap) is one of the first-line drugs for preventing cardiac remodeling in patients with heart failure, we hypothesized that Cap might prevent cardiac dysfunction induced by occlusal disharmony. Here, to test this idea, we used our bite-opening (BO) mouse model, which was developed by cementing a suitable appliance onto the mandibular incisor. Mice were divided into four groups: (1) Control, (2) BO, (3) Cap, and (4) BO + Cap. After 2 weeks, we evaluated cardiac function by echocardiography and confirmed that cardiac function was significantly decreased in the BO group compared to the control, while Cap ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and oxidative stress-induced myocardial damage in the BO group were significantly increased versus the control, and these increases were suppressed by Cap. Cardiac dysfunction induced by BO was associated with dual phosphorylation on PKCδ (Tyr-311/Thr-505), leading to activation of CaMKII with increased phosphorylation of RyR2 and phospholamban. Our results suggest that the RAS might play an important role in the development of cardiac diseases induced by occlusal anomalies.https://doi.org/10.1038/s41598-023-43099-6
spellingShingle Aiko Ito
Yoshiki Ohnuki
Kenji Suita
Ichiro Matsuo
Misao Ishikawa
Takao Mitsubayashi
Yasumasa Mototani
Kenichi Kiyomoto
Michinori Tsunoda
Akinaka Morii
Megumi Nariyama
Yoshio Hayakawa
Hiroshi Tomonari
Satoshi Okumura
Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
Scientific Reports
title Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
title_full Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
title_fullStr Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
title_full_unstemmed Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
title_short Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
title_sort effects of the angiotensin converting enzyme inhibitor captopril on occlusal disharmony induced cardiac dysfunction in mice
url https://doi.org/10.1038/s41598-023-43099-6
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