{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:53:12Z","timestamp":1791841992511,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303839\/2019\u20108"],"award-info":[{"award-number":["303839\/2019\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>6\u2010Nitrodopamine (6\u2010ND) is a novel endogenous catecholamine that has a potent relaxant action on vascular smooth muscle in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the basal release of 6\u2010ND and noradrenaline from rabbit\u2010isolated corpus cavernosum (RbCC) and its relaxing action on this tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rabbit corpus cavernosa were dissected and suspended in a 5\u2010mL organ bath containing oxygenated Krebs\u2010Henseleit's solution. 6\u2010ND and noradrenaline release was quantified by liquid chromatography coupled to tandem mass spectrometry. The relaxant activity of 6\u2010ND was assessed in RbCC strips pre\u2010contracted with endothelin\u20101 (10\u00a0nM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rabbit corpus cavernosum presented basal release of both 6\u2010ND (2.9\u00a0\u00b1\u00a00.8\u00a0ng\/mL, <jats:italic>n<\/jats:italic>\u00a0=\u00a012) and noradrenaline (1.7\u00a0\u00b1\u00a01.3\u00a0ng\/mL, <jats:italic>n<\/jats:italic>\u00a0=\u00a012). The 6\u2010ND release was reduced by pre\u2010treatment with N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME) (100 \u00b5M), whereas that of noradrenaline was unaffected. Tetrodotoxin (TTX, 1 \u00b5M) abolished the noradrenaline release but had no effect on 6\u2010ND release, indicating a non\u2010neurogenic origin for 6\u2010ND. 6\u2010ND and the selective dopamine D<jats:sub>2<\/jats:sub>\u2010agonist L\u2010741,626 caused concentration\u2010dependent RbCC relaxations (pEC<jats:sub>50<\/jats:sub> of 11\u00a0\u00b1\u00a00.15 and 11.15\u00a0\u00b1\u00a00.28, respectively). Pre\u2010treatment with either <jats:sc>l<\/jats:sc>\u2010NAME or the soluble guanylate cyclase inhibitor 1H\u2010[1,2,4] oxadiazolo[4,3\u2010a]quinoxalin\u20101\u2010on (ODQ) (100 \u00b5M) caused a rightward shift of the concentration\u2013response curve to 6\u2010ND, without affecting the L\u2010741,626 responses. In TTX (100\u00a0nM)\u2010pre\u2010treated preparations, neither <jats:sc>l<\/jats:sc>\u2010NAME nor ODQ shifted the 6\u2010ND concentration\u2013response curve. Dopamine, noradrenaline, and adrenaline caused concentration\u2010dependent RbCC contractions. Pre\u2010incubation with 6\u2010ND concentration\u2010dependently inhibited the dopamine\u2010induced contractions, without affecting those induced by either noradrenaline or adrenaline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>6\u2010Nitrodopamine is the most potent endogenous relaxant agent in RbCC ever described and represents a novel mechanism by which NO causes corpus cavernosum smooth muscle relaxation. The finding that 6\u2010ND acts as a truly selective dopamine D<jats:sub>2<\/jats:sub>\u2010receptor antagonist indicates that the balance of dopamine and 6\u2010ND release\/synthesis may be the main mechanism that modulates corpus cavernosum smooth muscle tonus in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13585","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T11:25:01Z","timestamp":1703849101000},"page":"1419-1428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["6\u2010Nitrodopamine is an endogenous mediator of the rabbit corpus cavernosum relaxation"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-7564","authenticated-orcid":false,"given":"Antonio Tiago","family":"Lima","sequence":"first","affiliation":[{"name":"Faculty of Medical Sciences Department of Pharmacology University of Campinas (UNICAMP)  Campinas 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