{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T03:04:58Z","timestamp":1778295898050,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"FWO-Vlaanderen"},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Geconcerteerde Onderzoeks Actie of Ghent University"}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The nitric oxide (NO), soluble guanylate cyclase (sGC), and cyclic guanosine monophosphate (cGMP) pathway is the leading pathway in penile erection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To assess erectile function in a mouse model in which sGC is deficient in heme (apo-sGC) and unresponsive to NO.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mutant mice (sGC\u03b21ki\/ki) that express an sGC enzyme that retains basal activity but fails to respond to NO because of heme deficiency (apo-sGC) were used. Isolated corpora cavernosa from sGC\u03b21ki\/ki and wild-type mice were mounted in\u00a0vitro for isometric tension recordings in response to sGC-dependent and -independent vasorelaxant agents. In addition, the erectile effects of some of these agents were tested in\u00a0vivo at intracavernosal injection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>In\u00a0vitro and in\u00a0vivo recordings of erectile responses in sGC\u03b21ki\/ki and wild-type mice after stimulation with sGC-dependent and -independent vasorelaxant agents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NO-induced responses were abolished in sGC\u03b21ki\/ki mice in\u00a0vitro and in\u00a0vivo. The ability of the heme-dependent, NO-independent sGC stimulator BAY 41-2272 to relax the corpora cavernosa was markedly attenuated in sGC\u03b21ki\/ki mice. In contrast, the relaxation response to the heme- and NO-independent sGC activator BAY 58-2667 was significantly enhanced in sGC\u03b21ki\/ki mice. The relaxing effect of sGC-independent vasorelaxant agents was similar in wild-type and sGC\u03b21ki\/ki mice, illustrating that the observed alterations in vasorelaxation are limited to NO-sGC-cGMP\u2013mediated processes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results suggest that sGC is the sole target of NO in erectile physiology. Furthermore, this\u00a0study provides indirect evidence that, in addition to sGC\u03b11\u03b21, sGC\u03b12\u03b21 is important for erectile function. In addition, the significant relaxation observed in sGC\u03b21ki\/ki mice with the cumulative addition of the sGC\u00a0activator BAY 58-2667 indicates that sGC activators might offer value in treating erectile dysfunction.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2016.12.007","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T05:50:33Z","timestamp":1486101033000},"page":"196-204","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Erectile Dysfunction in Heme-Deficient Nitric Oxide\u2013Unresponsive Soluble Guanylate Cyclase Knock-In Mice"],"prefix":"10.1093","volume":"14","author":[{"given":"Kelly","family":"Decaluw\u00e9","sequence":"first","affiliation":[{"name":"Department of Pharmacology \u00a0 , Ghent , Belgium"},{"name":"Ghent University \u00a0 , Ghent , 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