Non‐adrenergic Vasoconstriction of Human Blood Vessels to the Trace Amine, β‐Phenylethylamine

Abstract

Trace amines, such as β‐phenylethylamine (PEA), cause vasoconstriction in animal blood vessels not by indirect sympathomimetic actions but via trace amine‐associated receptors (TAARs). Functional studies were therefore performed on human arteries and veins surplus to coronary artery by‐pass graft (CABG) surgery to establish whether they constrict to PEA and if so whether they are adrenoceptor‐mediated. Internal mammary artery or saphenous vein rings were set up in organ baths containing Kreb's bicarbonate solution at 37±0.5°C gassed with O2:CO2 (95:5) under class 2 containment conditions. 1.5 g resting tension was applied and isometric contraction measured using a computerized Power Lab, Chart 5 data acquisition system (ADInstruments). Cumulative concentration‐response curves (CRC) were obtained for β‐phenylethylamine hydrochloride. Contractions were measured by subtracting baseline tension from plateau responses and expressed as a percentage of the contraction to KCl (60mM) added at the end. Responses were compared by Student's paired t‐test, P≤0.05 indicating significance. PEA showed concentration‐related contractions that were significantly greater at the maximum in the artery (1.53±0.31g, n=9) than the vein (0.55±0.18g, n=10). However, when plotted as % of the KCl maximum contraction, the maximum responses were not significantly different (vein 66.7±9.5%; artery 74.7±4.6% at 3×10−3M), indicating the overall greater contractility of this artery. PEA showed slowly developing contractions in both tissues which reached plateau effect after about 20 min. The reference α‐adrenoceptor agonist, phenylephrine, showed a much more rapid contraction, which was not sustained. In the saphenous vein, PEA (62.8±10.7%KCl) and phenylephrine (61.4±9.7%KCl, n=4) displayed the same maximum responses at 3×10−3M and 3×10−4M respectively, but phenylephrine was more potent. The α1‐adrenoceptor antagonist, prazosin (1μM) dissolved in 1 in 10 DMSO, blocked the responses to phenylephrine in the mammary artery but did not affect the contractions to PEA. Similarly, in the saphenous vein, prazosin (1μM) did not block the contractions to PEA. The DMSO vehicle for prazosin had no effect on PEA in mammary artery or saphenous vein. Thus, the indirect sympathomimetic and trace amine, PEA, has been shown to cause substantial vasoconstriction of human saphenous vein and mammary artery, which would explain its vasopressor actions in humans. This response however was not mediated via α1‐adrenoceptors, but was likely due to stimulation of TAARs.