Renal artery responses to trace amines: Multiple and differential mechanisms of action.

Purpose: The rise in consumption of dietary supplements containing the trace amines p-tyramine, p-synephrine and p-octopamine has been associated with cardiovascular side effects. Since renal blood flow plays an important role in blood pressure regulation, this study investigated the mechanisms of action of these trace amines on isolated porcine renal arteries.
Main Methods: Contractile responses to amines were investigated in noradrenaline-depleted rings of porcine main renal arteries in the absence and presence of the α ₁ -adrenoceptor antagonist, prazosin (1 μM), β-adrenoceptor antagonist, propranolol (1 μM), or the trace amine-associated receptor (TAAR-1) antagonist, EPPTB (RO-5212773; 100 nM or 100 μM).
Key Findings: All three amines induced constrictor responses of similar magnitude and potency. However, their mechanisms of action on the renal artery appeared to differ. Depleting endogenous noradrenaline stores significantly reduced maximum responses to tyramine and synephrine, but less for octopamine. When direct responses were examined after depleting tissues of noradrenaline, responses to synephrine and octopamine, but not tyramine, were reduced in the presence of prazosin(1 μM) and potentiated in the presence of propranolol (1 μM) or L-NNA (100 μM). Generally, vasoconstrictor responses remaining after noradrenaline-depletion and α-adrenoceptor blockade were not affected by the TAAR-1 antagonist EPPTB (0.1-100 μM), although responses to low concentration of synephrine and octopamine were enhanced by this antagonist.
Significance: Tyramine appears to mediate constriction of the renal artery mainly via an indirect sympathomimetic mechanism, whereas synephrine and octopamine exert additional direct effects on α ₁ -adrenoceptors and possibly contractile TAAR (not TAAR-1). The two amines also activate simultaneous inhibitory responses via β-adrenoceptors, TAAR-1 and nitric oxide release.
(Copyright © 2021. Published by Elsevier Inc.)