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Okinawa","award":["MOST110-2314-B-038-107-MY"],"award-info":[{"award-number":["MOST110-2314-B-038-107-MY"]}]},{"name":"Development of Internal Medicine in Okinawa","award":["MOST110-2314-B-016-037-MY3"],"award-info":[{"award-number":["MOST110-2314-B-016-037-MY3"]}]},{"name":"Development of Internal Medicine in Okinawa","award":["MND-MAB-D-112098"],"award-info":[{"award-number":["MND-MAB-D-112098"]}]},{"name":"Development of Internal Medicine in Okinawa","award":["CGH-MR-A11109"],"award-info":[{"award-number":["CGH-MR-A11109"]}]},{"name":"Development of Internal Medicine in Okinawa","award":["2-02-005"],"award-info":[{"award-number":["2-02-005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg\/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN\u2013RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1\/ET-A receptor\/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.<\/jats:p>","DOI":"10.3390\/ijms231910993","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T22:36:44Z","timestamp":1663713404000},"page":"10993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of Endothelin-1 in Right Atrial Arrhythmogenesis in Rabbits with Monocrotaline-Induced Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"23","author":[{"given":"Yen-Yu","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Cardiology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan"},{"name":"School of Medicine, Fu-Jen Catholic University, New Taipei City 24257, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong-Jhih","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Chang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsun","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan"},{"name":"Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-6249","authenticated-orcid":false,"given":"Satoshi","family":"Higa","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 901-2131, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ann","family":"Chen","sequence":"additional","affiliation":[{"name":"Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-4491","authenticated-orcid":false,"given":"Yi-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan"},{"name":"Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S0008-6363(98)00153-9","article-title":"The discovery of endothelins","volume":"39","author":"Masaki","year":"1998","journal-title":"Cardiovasc. 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