Non-adrenergic vasoconstriction and vasodilatation of guinea-pig aorta by β-phenylethylamine and amphetamine - Role of nitric oxide determined with L-NAME and NO scavengers

Abstract

Sympathomimetic and trace amines, including β-phenylethylamine (PEA) and amphetamine, increase blood pressure and constrict isolated blood vessels. By convention this is regarded as a sympathomimetic response, however, recent studies suggest trace amine-associated receptor (TAAR) involvement. There is also uncertainty whether these amines also release nitric oxide (NO) causing opposing vasodilatation. These questions were addressed in guinea-pig isolated aorta, a species not previously examined. Guinea-pig aortic rings were set up to measure contractile tension. Cumulative concentration-response curves were constructed for the reference α-adrenoceptor agonist, phenylephrine, PEA or d-amphetamine before and in the presence of vehicles, the α₁-adrenoceptor antagonist, prazosin (1µM), the nitric oxide synthase inhibitor, N^ω-nitro-L-arginine (L-NAME), or NO scavengers, curcumin and astaxanthin. Prazosin inhibited phenylephrine contractions with low affinity consistent with α_1L-adrenoceptors. However, PEA and amphetamine were not antagonised, indicating non-adrenergic responses probably via TAARs. L-NAME potentiated contractions to PEA both in the absence and presence of prazosin, indicating that PEA releases NO to cause underlying opposing vasodilatation, independent of α₁-adrenoceptors. L-NAME also potentiated amphetamine and phenylephrine. PEA was potentiated by the NO scavenger astaxanthin but less effectively. Curcumin, an active component of turmeric, however, inhibited PEA. Trace amines therefore constrict blood vessels non-adrenergically with an underlying NO-mediated non-adrenergic vasodilatation. This has implications in the pressor actions of these amines when NO is compromised.

Keywords: 2-phenylethylamine hydrochloride (PubChem CID: 1001); Amphetamine; Astaxanthin (PubChem CID: 5281224); Curcumin; Curcumin (PubChem CID: 969516); Guinea-pig aorta; L-NAME (PubChem CID: 74764530); L-phenylephrine hydrochloride (PubChem CID: 5284443); NO-scavengers; Nitric oxide; Prazosin hydrochloride (PubChem CID: 68546); d-Amphetamine hydrochloride (PubChem CID: 5826); β-phenylethylamine.