{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T10:21:30Z","timestamp":1777285290153,"version":"3.51.4"},"reference-count":38,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22ama121050j0001"],"award-info":[{"award-number":["22ama121050j0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K20622"],"award-info":[{"award-number":["20K20622"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006680","name":"Takeda Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006680","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004180","name":"NTT Research, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:p> Accentuated antagonism refers to a phenomenon in which the vagal effect on heart rate (HR) is augmented by background sympathetic tone. The dynamic aspect of accentuated antagonism remains to be elucidated during different levels of vagal nerve stimulation (VNS) intensity. We performed VNS on anesthetized rats ( n = 8) according to a binary white noise signal with a switching interval of 500 ms at three different stimulation rates (low-intensity: 0\u201310 Hz, moderate-intensity: 0\u201320 Hz, and high-intensity: 0\u201340 Hz). The transfer function from VNS to HR was estimated with and without concomitant tonic sympathetic nerve stimulation (SNS) at 5 Hz. The asymptotic low-frequency (LF) gain (in beats\/min\/Hz) of the transfer function increased with SNS regardless of the VNS rate [low-intensity: 3.93\u2009\u00b1\u20090.70 vs. 5.82\u2009\u00b1\u20090.65 ( P = 0.021), moderate-intensity: 3.87\u2009\u00b1\u20090.62 vs. 5.36\u2009\u00b1\u20090.53 ( P = 0.018), high-intensity: 4.77\u2009\u00b1\u20090.85 vs. 7.39\u2009\u00b1\u20091.36 ( P = 0.011)]. Moreover, SNS slightly increased the ratio of high-frequency (HF) gain to the LF gain. These effects of SNS were canceled by the pretreatment of ivabradine, an inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels, in another group of rats ( n = 6). Although background sympathetic tone antagonizes the vagal effect on mean HR, it enables finer HR control by increasing the dynamic gain of the vagal HR transfer function regardless of VNS intensity. When interpreting the HF component of HR variability, the augmenting effect from background sympathetic tone needs to be considered. <\/jats:p>","DOI":"10.1152\/ajpregu.00229.2022","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T02:30:46Z","timestamp":1672108246000},"page":"R260-R270","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Dynamic accentuated antagonism of heart rate control during different levels of vagal nerve stimulation intensity in rats"],"prefix":"10.1152","volume":"324","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-1802","authenticated-orcid":false,"given":"Toru","family":"Kawada","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-912X","authenticated-orcid":false,"given":"Aimi","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akitsugu","family":"Nishiura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Midori","family":"Kakuuchi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-5482","authenticated-orcid":false,"given":"Meihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-4702","authenticated-orcid":false,"given":"Kazunori","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Saku","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.29.5.437"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1989.256.1.H142"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2010.053090"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12055"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.271.1.H288"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00368.2007"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00288.2019"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00057.2021"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1991.260.1.H300"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.1.H326"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2016.03.004"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2009.02.006"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/9781118032428"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.14326\/abe.8.110"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.694512"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15134"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1109\/EMBC.2012.6346797"},{"key":"B18","unstructured":"Glantz SA. Primer of Biostatistics (5th ed.). New York: McGraw-Hill, 2002. p. 92\u201395."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050763"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005673"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/351145a0"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767002-00003"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.5.832"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.2916119"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2008"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.2.H562"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.367ac.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2170\/physiolsci.RP011508"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.115.5.547"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-018-0636-2"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.11.115"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-3970-0_4"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.6.H2141"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2012.10.008"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/science.6166045"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-003-0953-9"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00660.2002"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1991.260.1.H118"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00229.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T22:06:01Z","timestamp":1675116361000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00229.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2,1]]}},"alternative-id":["10.1152\/ajpregu.00229.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00229.2022","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]},"assertion":[{"value":"2022-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-22","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}