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Recent evidence allowing longer contact with isolated immersed tissues indicates other mechanisms. The present study re-evaluates the mechanism of pressor responses to PEA in anaesthetised rats with longer exposure to infusions. Blood pressure and heart rate were monitored by cannulating a common carotid artery of anaesthetised male Sprague\u2013Dawley rats. Drugs were administered by bolus doses or by 20-min infusions via a cannulated jugular vein. Increases in blood pressure by bolus doses of the \u03b1-adrenoceptor agonist, phenylephrine, were converted to depressor responses by prazosin and therefore \u03b1-adrenoceptor-mediated. Pressor responses to bolus doses of PEA were reduced. PEA infusions yielded four-phase responses: An initial increase in pressure (phase 1) blocked by prazosin was due to \u03b1-adrenoceptor vasoconstriction and a secondary fall in pressure (phase 2) due to vasodilatation by nitric oxide release. A later pressure increase (phase 3), further elevated after infusion stopped (phase 4), was not attenuated by prazosin and therefore non-adrenergic. This study showed for the first time that the sympathomimetic amine, \u03b2-phenylethylamine, increases blood pressure by two mechanisms. The established indirect sympathomimetic mechanism applies to bolus dose administration. However, with prolonged exposure to infusions, an additional slow-onset sustained non-adrenergic blood pressure increase occurs, most likely mediated via trace amine-associated receptors (TAAR-1). This response will dominate with prolonged exposures in clinical practice. These results prompt a re-evaluation of established dogma on the indirect sympathomimetic mechanisms of these amines.<\/jats:p>","DOI":"10.1007\/s00210-024-03218-0","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T10:34:34Z","timestamp":1725618874000},"page":"2627-2639","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reappraisal of the mechanism of cardiovascular responses to sympathomimetic amines in anaesthetised rats: dual \u03b11-adrenoceptor and trace amine receptor mechanisms"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-2050","authenticated-orcid":false,"given":"Kenneth J.","family":"Broadley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"3218_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1111\/j.1474-8673.2004.00303.x","volume":"23","author":"AL Al-Motarreb","year":"2004","unstructured":"Al-Motarreb AL, Broadley KJ (2004) Coronary and aortic vasoconstriction by cathinone, the active constituent of khat. 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The work and its reporting were undertaken according to the principles for transparent reporting and scientific rigour of preclinical research as set out in the Basel Declaration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights and informed consent"}},{"value":"The author declares no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}