{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T02:39:35Z","timestamp":1768790375204,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,4,16]],"date-time":"2007-04-16T00:00:00Z","timestamp":1176681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>Donors of nitroxyl (HNO), the reduced congener of nitric oxide (NO), exert positive cardiac inotropy\/lusitropy<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>, due in part to their enhancement of Ca<jats:sup>2+<\/jats:sup>cycling into and out of the sarcoplasmic reticulum. Here we tested whether the cardiac action of HNO further involves changes in myofilament\u2013calcium interaction. Intact rat trabeculae from the right ventricle were mounted between a force transducer and a motor arm, superfused with Krebs\u2013Henseleit (K\u2010H) solution (pH 7.4, room temperature) and loaded iontophoretically with fura\u20102 to determine [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Sarcomere length was set at 2.2\u20132.3 \u03bcm. HNO donated by Angeli's salt (AS; Na<jats:sub>2<\/jats:sub>N<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) dose\u2010dependently increased both twitch force and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transients (from 50 to 1000 \u03bc<jats:sc>m<\/jats:sc>). Force increased more than [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transients, especially at higher doses (332 \u00b1 33%<jats:italic>versus<\/jats:italic>221 \u00b1 27%,<jats:italic>P<\/jats:italic>&lt; 0.01 at 1000 \u03bc<jats:sc>m<\/jats:sc>). AS\/HNO (250 \u03bc<jats:sc>m<\/jats:sc>) increased developed force without changing Ca<jats:sup>2+<\/jats:sup>transients at any given [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>(0.5\u20132.0 m<jats:sc>m<\/jats:sc>). During steady\u2010state activation, AS\/HNO (250 \u03bc<jats:sc>m<\/jats:sc>) increased maximal Ca<jats:sup>2+<\/jats:sup>\u2010activated force (<jats:italic>F<\/jats:italic><jats:sub>max<\/jats:sub>, 106.8 \u00b1 4.3<jats:italic>versus<\/jats:italic>86.7 \u00b1 4.2 mN mm<jats:sup>\u22122<\/jats:sup>,<jats:italic>n<\/jats:italic>= 7\u20138,<jats:italic>P<\/jats:italic>&lt; 0.01) without affecting Ca<jats:sup>2+<\/jats:sup>required for 50% activation (Ca<jats:sub>50<\/jats:sub>, 0.44 \u00b1 0.04<jats:italic>versus<\/jats:italic>0.52 \u00b1 0.04 \u03bc<jats:sc>m<\/jats:sc>, not significant) or the Hill coefficient (4.75 \u00b1 0.67<jats:italic>versus<\/jats:italic>5.02 \u00b1 1.1, not significant). AS\/HNO did not alter myofibrillar Mg\u2010ATPase activity, supporting an effect on the myofilaments themselves. The thiol reducing agent dithiothreitol (DTT, 5.0 m<jats:sc>m<\/jats:sc>) both prevented and reversed HNO action, confirming AS\/HNO redox sensitivity. Lastly, NO (from DEA\/NO) did not mimic AS\/HNO cardiac effects. Thus, in addition to reported changes in Ca<jats:sup>2+<\/jats:sup>cycling, HNO also acts as a cardiac Ca<jats:sup>2+<\/jats:sup>sensitizer, augmenting maximal force without altering actomyosin ATPase activity. This is likely to be due to modulation of myofilament proteins that harbour reactive thiolate groups that are targets of HNO.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.129254","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T03:56:11Z","timestamp":1172807771000},"page":"951-960","source":"Crossref","is-referenced-by-count":87,"title":["Nitroxyl increases force development in rat cardiac muscle"],"prefix":"10.1113","volume":"580","author":[{"given":"Tieying","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo Gabriele","family":"Tocchetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Katori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne M.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazareno","family":"Paolocci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Dong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,4,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.105.1.1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00163-7"},{"key":"e_1_2_5_4_1","first-page":"1","article-title":"The cross\u2010bridge cycle in muscle. 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