Dietary trace amine‐dependent vasoconstriction in porcine coronary artery

Abstract

Background and purpose: The dietary trace amines tyramine and b-phenylethylamine (b-PEA) can increase blood pressure. However, the mechanisms involved in the vascular effect of trace amines have not been fully established. The purpose of this study was to evaluate whether trace amine-dependent vasoconstriction was brought about by tyramine and b-PEA acting as indirect sympathomimetic agents, as previously assumed, or whether trace amine-dependent vasoconstriction could be mediated by recently discovered trace amine-associated (TAA) receptors. Experimental approach: The responses to p-tyramine and b-PEA were investigated in vitro in rings of the left anterior descending coronary arteries of pigs. Key results: p-Tyramine induced a concentration-dependent (0.1-3 mM) vasoconstriction. The maximum response and pD 2 value for p-tyramine was unaffected by endothelium removal or pre-treatment with antagonists for adrenoceptors, histamine, dopamine or 5-HT receptors. b-PEA also produced a concentration-dependent (0.3-10 mM) vasoconstriction which was unaffected by endothelium removal, b-adrenoceptor or 5-HT receptor antagonists. A substantial, but reduced, response to b-PEA was obtained in the presence of prazosin (a 1 -adrenoceptor antagonist), haloperidol (D 2 /D 3 dopamine receptor antagonist) or mepyramine (H 1 histamine receptor antagonist). The pD 2 value for b-PEA was unaffected by any of the antagonists tested. Conclusions and implications: Vasoconstriction induced by p-tyramine does not involve an indirect sympathomimetic effect, although vasoconstriction caused by b-PEA may occur, in part, by this mechanism. We therefore propose that trace aminedependent vasoconstriction is mediated by phenylethylamine-specific receptors, which are closely related to or identical to TAA receptors. These receptors could provide a target for new antihypertensive therapies.

Probiotics supplementation increases intestinal blood flow velocity in extremely low birth weight preterm infants

“…Explanation for such SMA BFV increase in the probiotic group could be potentially found in animal studies, 7,8 which investigated the role of probiotic-generated trace amines (tyramine and b-phenylethylamine). In guinea-pig and rat models, mesenteric vasculature, rings of aorta and coronary arteries were isolated and exposed to the gradually increasing concentrations of tyramine and b-phenylethylamine, leading to vasoconstriction of the aorta and coronary arteries and relaxation of the mesenteric vascular bed.…”

“…5 Recently, it has been reported that probiotics are a source of the trace amines, tyramine and b-phenylethylamine, which affect vasculature independently via recently described trace amineassociated receptors. 7,8 In animal models, amines exert differential effects on aorta/coronary arteries and mesenteric vasculature, causing relaxation of mesenteric vasculature and subsequent improvement in the intestinal blood flow. It has been well established that alterations in intestinal blood flow have an impact on tolerance to enteral feedings in preterm neonates.…”

Ractopamine, a Livestock Feed Additive, Is a Full Agonist at Trace Amine–Associated Receptor 1

“…Our results indicate that RAC, contrary to expectations, is not an agonist of the hb 2 AR but rather is a full agonist of the closely related mTAAR1. Since TAAR1-mediated signaling can influence cardiovascular tone (Fellows, 1947;Frascarelli et al, 2008;Herbert et al, 2008;Broadley, 2010;Fehler et al, 2010;Broadley et al, 2013) and behavior in several animal models (Miller, 2011;Revel et al, 2011;Achat-Mendes et al, 2012), our finding that RAC is a full mTAAR1 agonist constitutes a novel mechanism by which RAC can influence the physiology and behavior of pigs (Marchant-Forde et al, 2003;Poletto et al, 2009Poletto et al, , 2010a and other species. These findings should stimulate future studies to characterize the pharmacological, physiological, and behavioral actions of RAC in humans and other species exposed to this drug.…”

Dual excitatory and smooth muscle‐relaxant effect of β‐phenylethylamine on gastric fundus strips in rats

“…The pressor response that was induced by the trace amine tryptamine in mesenteric vessels was abolished by ketanserin and ritanserin, two 5‐hydroxytryptamine (5‐HT) receptor antagonists . In contrast, β‐PEA‐induced vasoconstriction in porcine coronary artery was unaffected by the 5‐HT receptor antagonist ketanserin …”