Trace amine-induced vasoconstriction of human mammary artery and saphenous vein

Broadley, Kenneth J. ORCID: https://orcid.org/0000-0002-3339-2050 and Mehta, Dheeraj 2023. Trace amine-induced vasoconstriction of human mammary artery and saphenous vein. Vascular Pharmacology 151 , 107191. 10.1016/j.vph.2023.107191

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Abstract

Sympathomimetic amines, including β-phenylethylamine (PEA), constrict animal blood vessels but their mechanism of action is not now thought to be through α-adrenoceptors and release of noradrenaline but via trace amine-associated receptors (TAARs). This information is not available for human blood vessels. Functional studies were therefore performed on human arteries and veins to establish whether they constrict to PEA and whether any constrictions are adrenoceptor-mediated. Isolated internal mammary artery or saphenous vein rings were set up in Kreb's-bicarbonate solution at 37 ± 0.5 °C gassed with O2:CO2 (95:5) under class 2 containment. Isometric contractions were measured and cumulative concentration-response curves for PEA or the α-adrenoceptor agonist, phenylephrine were established. PEA showed concentration-related contractions. The maximum was significantly greater in arteries (1.53 ± 0.31 g, n = 9) than veins (0.55 ± 0.18 g, n = 10), but not when plotted as % of KCl contractions. PEA showed slowly developing contractions plateauing at 17,3 ± 3.7 min in mammary artery. The reference α-adrenoceptor agonist, phenylephrine, exhibited more rapid onset (peak 5.0 ± 1.2 min) but non-sustained contractions. In saphenous veins, PEA (62.8 ± 10.7%) and phenylephrine (61.4 ± 9.7%, n = 4) displayed the same maximum, but phenylephrine was more potent. The α1-adrenoceptor antagonist, prazosin (1 μM), blocked phenylephrine contractions of mammary arteries but not PEA contractions in either vessel. PEA causes substantial vasoconstriction of human saphenous vein and mammary artery, which explains its vasopressor actions. This response, however, was not mediated via α1-adrenoceptors, but likely due to TAARs. The classification of PEA as a sympathomimetic amine on human blood vessels is therefore no longer valid and requires revision.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	15371891
Date of First Compliant Deposit:	2 August 2023
Date of Acceptance:	29 June 2023
Last Modified:	03 Aug 2023 10:38
URI:	https://orca.cardiff.ac.uk/id/eprint/161429

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