{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:08:38Z","timestamp":1790935718919,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2000,10,27]]},"abstract":"<jats:p>\n                    <jats:italic>Abstract<\/jats:italic>\n                    \u2014Both cGMP-dependent and -independent mechanisms have been implicated in the regulation of vascular tone by NO. We analyzed acetylcholine (ACh)- and NO-induced relaxation in pressurized small arteries and aortic rings from wild-type (wt) and cGMP kinase I\u2013deficient (cGKI\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) mice. Low concentrations of NO and ACh decreased the spontaneous myogenic tone in wt but not in cGKI\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    arteries. However, contractions of cGKI\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    arteries and aortic rings were reduced by high concentrations (10 \u03bcmol\/L) of 2-(\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    -diethylamino)-diazenolate-2-oxide (DEA-NO). Iberiotoxin, a specific blocker of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    ) channels, only partially prevented the relaxation induced by DEA-NO or ACh in pressurized vessels and aortic rings. DEA-NO increased the activity of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels only in vascular smooth muscle cells isolated from wt cGKI\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice. These results suggest that low physiological concentrations of NO decrease vascular tone through activation of cGKI, whereas high concentrations of DEA-NO relax vascular smooth muscle independent of cGKI and BK\n                    <jats:sub>Ca<\/jats:sub>\n                    . NO-stimulated, cGKI-independent relaxation was antagonized by the inhibition of soluble guanylyl cyclase or cAMP kinase (cAK). DEA-NO increased cGMP to levels that are sufficient to activate cAK. cAMP-dependent relaxation was unperturbed in cGKI\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    vessels. In conclusion, low concentrations of NO relax vessels by activation of cGKI, whereas in the absence of cGKI, NO can relax small and large vessels by cGMP-dependent activation of cAK.\n                  <\/jats:p>","DOI":"10.1161\/01.res.87.9.825","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:52:16Z","timestamp":1339447936000},"page":"825-830","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":193,"title":["Mechanisms of NO\/cGMP-Dependent Vasorelaxation"],"prefix":"10.1161","volume":"87","author":[{"given":"Matthias","family":"Sausbier","sequence":"first","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Schubert","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Voigt","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hirneiss","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Korth","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kleppisch","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ruth","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; and Abteilung Pharmakologie fu\u0308r Pharmazeuten, Universita\u0308tskrankenhaus Eppendorf (M.K.), Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Hofmann","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Pharmakologie und Toxikologie der TU Mu\u0308nchen (M.S., V.V., C.H., A.P., T.K., P.R., F.H.), Mu\u0308nchen, Germany; Institut fu\u0308r Physiologie der Universita\u0308t Rostock (R.S.), Rostock, Germany; 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