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

Autor: Aiko Ito, Yoshiki Ohnuki, Kenji Suita, Ichiro Matsuo, Misao Ishikawa, Yasumasa Mototani, Kenichi Kiyomoto, Michinori Tsunoda, Akinaka Morii, Megumi Nariyama, Yoshio Hayakawa, Hiroshi Tomonari, Satoshi Okumura
Rok vydání: 2022
DOI: 10.21203/rs.3.rs-2303432/v1
Popis: 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.
Databáze: OpenAIRE