{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:11:36Z","timestamp":1753884696074,"version":"3.41.2"},"reference-count":30,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitric oxide (NO) is thought to increase cardiac contractility by increasing cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>) during excitation. Alternatively, NO could increase the sensitivity of the contractile response to [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> (Ca<jats:sup>2+<\/jats:sup> sensitivity). Arginase regulates NO production by competing with NO synthase (NOS), and thus, arginase inhibition should increase cardiac contractility by increasing NO production. We hypothesized that arginase inhibition increases cardiac contractility by increasing both [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and Ca<jats:sup>2+<\/jats:sup> sensitivity. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and contractile (sarcomere length [SL] shortening) responses to electrical stimulation were measured simultaneously in isolated rat cardiomyocytes using an IonOptix system. In the same cardiomyocytes, measurements were obtained at baseline, following 3\u2010min exposure to an arginase inhibitor (<jats:italic>S<\/jats:italic>\u2010[2\u2010boronoethyl]\u2010<jats:sc>l<\/jats:sc>\u2010cysteine; BEC) and following 3\u2010min exposure to BEC plus a NOS inhibitor (<jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine\u2010methyl ester; <jats:sc>l<\/jats:sc>\u2010NAME). These responses were compared to time\u2010matched control cardiomyocytes that were untreated. Compared to baseline, BEC increased the amplitude and the total amount of evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>, and the extent and velocity of SL shortening in cardiomyocytes, whereas addition of <jats:sc>l<\/jats:sc>\u2010NAME mitigated these effects. The [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> at 50% contraction and relaxation were not different across treatment groups indicating no effect of BEC on Ca<jats:sup>2+<\/jats:sup> sensitivity. The [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and SL shortening responses in time\u2010matched controls did not vary with time. Arginase inhibition by BEC significantly increased the amplitude and the total amount of evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>, and the extent and velocity of SL shortening in cardiomyocytes, but did not affect Ca<jats:sup>2+<\/jats:sup> sensitivity. These effects of BEC were mitigated by <jats:sc>l<\/jats:sc>\u2010NAME. Together, these results indicate an effect of NO on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> responses that then increase the contractile response of cardiomyocytes.<\/jats:p>","DOI":"10.14814\/phy2.15396","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T07:27:05Z","timestamp":1658474825000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of arginase inhibition on myocardial Ca<sup>2+<\/sup> and contractile responses"],"prefix":"10.14814","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-4188","authenticated-orcid":false,"given":"Jin Sun","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Soo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cole","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-9424","authenticated-orcid":false,"given":"Gary","family":"Sieck","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/416337a"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.5.C1424"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000092948.04444.C7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.055913"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000166837.78559.93"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04638.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00143-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.186015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01104.2005"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00549.2001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-011-2257-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404136101"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000078171.52542.9E"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2012.145"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91393.2008"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.014126"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113196660746"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000088351.58510.21"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00259-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt036"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-7757-9_8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00840.2015"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.04.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506589103"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1693"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00367.2007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5348.234"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.09.076"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.07.015"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15396","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.15396","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15396","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:36:57Z","timestamp":1704879417000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":30,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.14814\/phy2.15396"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15396","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"type":"print","value":"2051-817X"},{"type":"electronic","value":"2051-817X"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"2022-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15396"}}