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In apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice (<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub><jats:sup>His105Phe<\/jats:sup>knockin) both<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>isoforms (<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content><jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub><jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub>and<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content><jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub><jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub>) are heme\u2010deficient and can no longer be activated by<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>; these mice, showing decreased gastrointestinal nitrergic relaxation and decreased gastric emptying, can be considered as a model to study the consequence of heme\u2010oxidation in<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>. Our aim was to compare the influence of cinaciguat, on<jats:italic>in vitro<\/jats:italic>muscle tone of gastrointestinal tissues, and on gastric emptying in<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>and apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gastrointestinal smooth muscle strips were mounted in organ baths for isometric force recording and<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>levels were determined by enzyme immunoassay. Protein levels of<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>subunits were assessed by immunoblotting. Gastric emptying was determined by phenol red recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Although protein levels of the<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>subunits were lower in gastrointestinal tissues of apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice, cinaciguat induced concentration\u2010dependent relaxations and increased<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>levels in apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>fundus and colon to a similar or greater extent than in<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>mice. The<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>inhibitor<jats:styled-content style=\"fixed-case\">ODQ<\/jats:styled-content>increased cinaciguat\u2010induced relaxations and<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>levels in<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>fundus and colon. In apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>antrum, pylorus and jejunum, cinaciguat was not able to induce relaxations. Cinaciguat did not improve delayed gastric emptying in apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Cinaciguat relaxes the fundus and colon efficiently when<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>is in the heme\u2010free condition; the non\u2010effect of cinaciguat in pylorus explains its inability to improve the delayed gastric emptying in apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12424","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T02:42:00Z","timestamp":1410230520000},"page":"1573-1585","source":"Crossref","is-referenced-by-count":1,"title":["Influence of cinaciguat on gastrointestinal motility in apo\u2010<scp>sGC<\/scp>mice"],"prefix":"10.1111","volume":"26","author":[{"given":"Sarah M. 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