{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:40:09Z","timestamp":1791394809532,"version":"4.3.3"},"reference-count":67,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,9,4]]},"abstract":"<jats:p>Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA\u2013null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P &amp;lt; 0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)\u2013null mice released much more NE (i.e., a 275% increase; P &amp;lt; 0.05). Furthermore, vasa deferentia from t-PA\u2013null mice were hyporesponsive to EFS (P &amp;lt; 0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1\u2013null mice were much more responsive (P &amp;lt; 0.05). Coronary NE overflow from hearts subjected to ischemia\/reperfusion was much smaller in t-PA\u2013null than in WT control mice (P &amp;lt; 0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P &amp;lt; 0.05) in t-PA\u2013null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia\/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.<\/jats:p>","DOI":"10.1084\/jem.20060077","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T02:10:28Z","timestamp":1156817428000},"page":"2191-2200","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["The plasminogen activator system modulates sympathetic nerve function"],"prefix":"10.1084","volume":"203","author":[{"given":"Ulrich","family":"Schaefer","sequence":"first","affiliation":[{"name":"1Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Machida","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Vorlova","sequence":"additional","affiliation":[{"name":"2Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Strickland","sequence":"additional","affiliation":[{"name":"2Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Levi","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,8,28]]},"reference":[{"key":"2023072513423835700_BIB1","first-page":"855","volume":"144","year":"1994","journal-title":"Am. 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