{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:38:38Z","timestamp":1792733918785,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 2060 projects FE 438\/5\u20102 and FE 438\/6\u20102"],"award-info":[{"award-number":["FOR 2060 projects FE 438\/5\u20102 and FE 438\/6\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>cGMP evokes arteriolar vasorelaxation and is generated in smooth muscle by the soluble guanylyl cyclase (sGC) stimulated by endothelial NO. Phosphodiesterases (PDEs) degrade cGMP and may contribute in diameter regulation. We examined arteriolar cGMP levels in real\u2010time in\u00a0vivo upon NO and acetylcholine (ACh) and effects of PDE inhibition. Changes in cGMP were measured by FRET using the indicator protein cGi500. Arterioles in the cremaster muscle of anesthetized mice expressing cGi500 were exposed for imaging. They were stimulated with various NO donors (DEA\/NO, SNP, SNAP) and ACh with or without PDE inhibition (non\u2010specific: IBMX; PDE\u20105 specific: sildenafil). Furthermore, dilations induced by ACh and SNP were studied in sGC\u2010deficient mice. DEA\/NO and SNAP led to a fast, concentration\u2010dependent rise of fluorescence ratio of cGi500 (by 4.0% at 10\u2009\u03bcmol\/L), that declined on removal slowly. These ratio changes indicated cGMP increases as verified by inhibition of the sGC using ODQ. PDE inhibition increased cGMP levels slowly despite NO synthase inhibition. However, it did not amplify NO\u2010induced ratio increases, but the decline after drug removal was decelerated. Interestingly, ACh did not modify cGMP levels and dilations were not impaired in sGC\u2010deficient mice. FRET\u2010based imaging allows reliable real\u2010time assessment of arteriolar cGMP levels in\u00a0vivo. PDE activity does not limit the amplitude, but the duration of cGMP signaling after stimulation. Furthermore, we conclude that ACh does not release endothelial NO in murine arterioles. Preliminary experiments demonstrate that simultaneous measurement of cGMP and diameter is feasible using mice with expression of cGi500 in smooth muscle cells.<\/jats:p>","DOI":"10.1111\/apha.70317","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:22:10Z","timestamp":1790562130000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>cGMP<\/scp>\n                    Signaling in Arterioles Revealed by\n                    <scp>FRET<\/scp>\n                    \u2010Based Real\u2010Time Measurement in Mice In\u00a0Vivo"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5098-4373","authenticated-orcid":false,"given":"Lukas","family":"Thiele","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Partner Site North German Centre for Cardiovascular Research (DZHK)  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjestine","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Partner Site North German Centre for Cardiovascular Research (DZHK)  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4139-079X","authenticated-orcid":false,"given":"Martin","family":"Thunemann","sequence":"additional","affiliation":[{"name":"Interfakult\u00e4res Institut f\u00fcr Biochemie Universit\u00e4t T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-3948","authenticated-orcid":false,"given":"Andreas","family":"Friebe","sequence":"additional","affiliation":[{"name":"Physiologisches Institut Julius\u2010Maximilians Universit\u00e4t  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2148-8773","authenticated-orcid":false,"given":"Susanne","family":"Feil","sequence":"additional","affiliation":[{"name":"Interfakult\u00e4res Institut f\u00fcr Biochemie Universit\u00e4t T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7335-4841","authenticated-orcid":false,"given":"Robert","family":"Feil","sequence":"additional","affiliation":[{"name":"Interfakult\u00e4res Institut f\u00fcr Biochemie Universit\u00e4t T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-0399","authenticated-orcid":false,"given":"Cor","family":"de Wit","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Partner Site North German Centre for Cardiovascular Research (DZHK)  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5444.1583"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.153981"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2015"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.1.37"},{"key":"e_1_2_9_8_1","first-page":"74","article-title":"A Unique Role of NO in the Control of Blood Flow","volume":"14","author":"Pohl U.","year":"1999","journal-title":"News in Physiological Sciences"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.12.017"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2010"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.10.1513"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14651"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)45621-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.8.3203"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.3.1188"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80604-2"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070348"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301063"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15500"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00060.2009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.265835"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609778104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704103"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00394"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(25)10233-2"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2592"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102650499"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(03)00046-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511803200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019240"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-3992"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-442277"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16230"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.165894"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000238377.08219.0c"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.846634"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000147661.80059.ca"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70193"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042287"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0411"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06638-8"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-021-02607-1"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000088101"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70317","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.70317","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:00:43Z","timestamp":1792731643000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.70317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/apha.70317"],"URL":"https:\/\/doi.org\/10.1111\/apha.70317","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70317"}}