{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:27:08Z","timestamp":1740119228942,"version":"3.37.3"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,15]],"date-time":"2020-02-15T00:00:00Z","timestamp":1581724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ryanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) leads to malignant hyperthermia, and in cardiac muscle (RyR2) triggers cardiac arrhythmias. We hypothesized that RyR dysfunction in vascular smooth muscle could increase vascular resistance and hypertension, and may contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension and AF inducibility in spontaneously hypertensive rats (SHR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male SHR (16 weeks old) were randomized into vehicle- (n = 10) and dantrolene-treated (10 mg\/kg\/day, n = 10) groups for 4 weeks. Wistar Kyoto (WKY, n = 11) rats served as controls. Blood pressures (BP) were monitored before and during the 4-week treatment. After 4-week treatment, direct BP, echocardiography, and hemodynamics were recorded. AF inducibility tests were performed in vivo at baseline and repeated under sympathetic stimulation (SS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with WKY, SHR had significantly higher BP throughout the experimental period. Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212 \u00b1 9 mm Hg in vehicle group vs. 208 \u00b1 16 mm Hg in dantrolene group, P &amp;gt; 0.05). AF inducibility was very low and not significantly different between 5-month-old WKY and SHR at baseline. However, under SS, AF inducibility and duration were significantly increased in SHR (20% in WKY vs. 60% in SHR-vehicle, P&amp;lt;0.05). Dantrolene treatment significantly attenuated AF inducibility under SS in SHR (60% in vehicle vs. 20% in dantrolene, P &amp;lt; 0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Stabilizing RyR with chronic dantrolene treatment does not affect hypertension development in SHR. SHR has increased vulnerability to AF induction under SS, which can be attenuated with dantrolene treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpaa021","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T20:10:37Z","timestamp":1581451837000},"page":"407-413","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Dantrolene Treatment Does Not Affect Hypertension, but Attenuates Sympathetic Stimulation Enhanced Atrial Fibrillation Inducibility in SHR"],"prefix":"10.1093","volume":"33","author":[{"given":"Jae S","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Migirov","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Martin","family":"Gerdes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-2705","authenticated-orcid":false,"given":"Youhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine , Old Westbury, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,2,15]]},"reference":[{"key":"2022100612393596600_CIT0001","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/cphy.c160011","article-title":"Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles","volume":"7","author":"Tykocki","year":"2017","journal-title":"Compr Physiol"},{"key":"2022100612393596600_CIT0002","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: a review","volume":"10","author":"Rosenberg","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"2022100612393596600_CIT0003","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/ALN.0000000000001878","article-title":"Malignant hyperthermia in the post-genomics era: new perspectives on an old concept","volume":"128","author":"Riazi","year":"2018","journal-title":"Anesthesiology"},{"key":"2022100612393596600_CIT0004","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1161\/01.CIR.103.2.196","article-title":"Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia","volume":"103","author":"Priori","year":"2001","journal-title":"Circulation"},{"key":"2022100612393596600_CIT0005","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.hrthm.2016.09.014","article-title":"Antiarrhythmic effects of dantrolene in human diseased cardiomyocytes","volume":"14","author":"Hartmann","year":"2017","journal-title":"Heart Rhythm"},{"key":"2022100612393596600_CIT0006","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1016\/j.jacc.2009.02.032","article-title":"Diastolic release of calcium from the sarcoplasmic reticulum: a potential target for treating triggered arrhythmias and heart failure","volume":"53","author":"Shannon","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2022100612393596600_CIT0007","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1161\/CIRCULATIONAHA.104.507921","article-title":"Defective regulation of interdomain interactions within the ryanodine receptor plays a key role in the pathogenesis of heart failure","volume":"111","author":"Oda","year":"2005","journal-title":"Circulation"},{"key":"2022100612393596600_CIT0008","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1161\/HYPERTENSIONAHA.111.173500","article-title":"Ryanodine receptor type 2 is required for the development of pressure overload-induced cardiac hypertrophy","volume":"58","author":"Zou","year":"2011","journal-title":"Hypertension"},{"key":"2022100612393596600_CIT0009","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1161\/ATVBAHA.107.144808","article-title":"Removal of FKBP12\/12.6 from endothelial ryanodine receptors leads to an intracellular calcium leak and endothelial dysfunction","volume":"27","author":"Long","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2022100612393596600_CIT0010","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.jacc.2009.01.065","article-title":"Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor","volume":"53","author":"Kobayashi","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2022100612393596600_CIT0011","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1253\/circj.CJ-10-0680","article-title":"Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S\/+) knock-in mouse model","volume":"74","author":"Kobayashi","year":"2010","journal-title":"Circ J"},{"key":"2022100612393596600_CIT0012","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.cardfail.2018.05.008","article-title":"Failing hearts are more vulnerable to sympathetic, but not vagal stimulation-induced, atrial fibrillation-ameliorated with dantrolene treatment","volume":"24","author":"Delfiner","year":"2018","journal-title":"J Card Fail"},{"key":"2022100612393596600_CIT0013","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cardfail.2014.10.003","article-title":"Thyroid hormone replacement therapy attenuates atrial remodeling and reduces atrial fibrillation inducibility in a rat myocardial infarction-heart failure model","volume":"20","author":"Zhang","year":"2014","journal-title":"J Card Fail"},{"key":"2022100612393596600_CIT0014","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/CIRCEP.113.000502","article-title":"Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats","volume":"6","author":"Zhang","year":"2013","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022100612393596600_CIT0015","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.3389\/fphys.2018.01018","article-title":"Inositol 1,4,5-trisphosphate receptors in hypertension","volume":"9","author":"Eid","year":"2018","journal-title":"Front Physiol"},{"key":"2022100612393596600_CIT0016","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1161\/01.HYP.29.6.1322","article-title":"Alterations in calcium stores in aortic myocytes from spontaneously hypertensive rats","volume":"29","author":"C\u00f4rtes","year":"1997","journal-title":"Hypertension"},{"key":"2022100612393596600_CIT0017","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1001\/jama.1994.03510350050036","article-title":"Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham heart study","volume":"271","author":"Benjamin","year":"1994","journal-title":"JAMA"},{"key":"2022100612393596600_CIT0018","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1161\/CIRCULATIONAHA.111.067306","article-title":"Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation","volume":"125","author":"Voigt","year":"2012","journal-title":"Circulation"},{"key":"2022100612393596600_CIT0019","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1161\/01.CIR.0000162461.67140.4C","article-title":"Defective cardiac ryanodine receptor regulation during atrial fibrillation","volume":"111","author":"Vest","year":"2005","journal-title":"Circulation"},{"key":"2022100612393596600_CIT0020","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1161\/01.HYP.0000257123.95372.ab","article-title":"Increased susceptibility to atrial tachyarrhythmia in spontaneously hypertensive rat hearts","volume":"49","author":"Choisy","year":"2007","journal-title":"Hypertension"},{"key":"2022100612393596600_CIT0021","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/cvr\/cvv045","article-title":"Early subcellular Ca2+ remodelling and increased propensity for Ca2+ alternans in left atrial myocytes from hypertensive rats","volume":"106","author":"Pluteanu","year":"2015","journal-title":"Cardiovasc Res"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajh\/advance-article-pdf\/doi\/10.1093\/ajh\/hpaa021\/32894121\/hpaa021.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/33\/5\/407\/46351621\/ajh_33_5_407.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/33\/5\/407\/46351621\/ajh_33_5_407.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T13:10:31Z","timestamp":1665061831000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/article\/33\/5\/407\/5736361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,15]]},"references-count":21,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,2,15]]},"published-print":{"date-parts":[[2020,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpaa021","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"type":"print","value":"0895-7061"},{"type":"electronic","value":"1941-7225"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,2,15]]}}}