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Basal release of both dopamine and 6-ND is present in human isolated umbilical cord vessels, human popliteal vessels, nonhuman primate vessels, and reptilia aortas. The 6-ND basal release was significantly reduced when the tissues were treated with N\n                    <jats:sup>\u03c9<\/jats:sup>\n                    -nitro-l-arginine methyl ester and virtually abolished when the endothelium was mechanically removed. 6-Nitrodopamine is a potent vasodilator, and the mechanism of action responsible for this effect is the antagonism of dopamine D\n                    <jats:sub>2<\/jats:sub>\n                    -like receptors. As a vasodilator, 6-ND constitutes a novel mechanism by which nitric oxide modulates vascular tone. The basal release of 6-ND was substantially decreased in endothelial nitric oxide synthase knockout (eNOS\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice and not altered in neuronal nitric oxide synthase knockout (nNOS\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, indicating a nonneurogenic source for 6-ND in the heart. Indeed, in rat isolated right atrium, the release of 6-ND was not affected when the atria were treated with tetrodotoxin. In the rat isolated right atrium, 6-ND is the most potent endogenous positive chronotropic agent, and in Langendorff\u2019s heart preparation, it is the most potent endogenous positive inotropic agent. The positive chronotropic and inotropic effects of 6-ND are antagonized by \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -adrenoceptor antagonists at concentrations that do not affect the effects induced by noradrenaline, adrenaline, and dopamine, indicating that blockade of the 6-ND receptor is the major modulator of heart chronotropism and inotropism. The review proposes that endothelium-derived catecholamines may constitute a major mechanism for control of vascular tone and heart functions, in contrast to the overrated role attributed to the autonomic nervous system.\n                  <\/jats:p>","DOI":"10.1152\/physiol.00020.2023","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T14:12:50Z","timestamp":1698156770000},"page":"44-59","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System"],"prefix":"10.1152","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-3220","authenticated-orcid":false,"given":"Roberto","family":"Zatz","sequence":"first","affiliation":[{"name":"Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo, 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