Estudo farmacológico do efeito vasorrelaxante da beta-feniletilamina em aorta isolada de rato

Abstract

Beta-phenylethylamine (β - FEA) is an amine possessing a chemical resemblance with 1-nitro-2-phenylethane, which contains a nitro group in place of the amine group. 1- Nitro-2-phenylethane induces vasodilation by stimulating guanylate cyclase. β-FEA is a trace amine because it is found in low concentrations in mammalian tissues. The aim of this study was to evaluate the potential vasorelaxing effects of β-FEA in isolated aorta of Wistar rats. Isometric contractions were carried out from rings of isolated aorta and recorded in a data acquisition system. In endothelium-intact aortic preparations kept at baseline tonus, β-FEA (10-3000 µM) induced concentration-dependent contractile effect, and removal of the vascular endothelium potentiated such effect. Otherwise, in endothelium-intact aortic preparations precontracted with the α1-adrenergic agonist phenylephrine, β-FEA (1-3000 µM) induced relaxation with EC50 value of 85.61 [70.81 to 101.5] µM. However, only slightly relaxed the contraction induced by K+ (60 mM) or by the thromboxane A2 mimetic U-46619(0.3 µM) and not relaxed the contraction induced by the α2-adrenoceptor agonist clonidine(100 µM). Vasorelaxing effect of β- FEA was significantly reduced (p <0.05, Holm-Sidak test) by mechanical removal of endothelium and by previous treatment with L-NAME (100 µM), ODQ (10 µM), indomethacin (10 µM), TEA (5 mM) or 4-aminopyridine (1 mM), but not by propranolol (5 μM), MDL 12,330A (3 μM) or glibenclamide (10 µM). In a calcium free medium containing EGTA, the contractile response to phenylephrine was significantly reduced by β-FEA (100 μM). Moreover, β-FEA (300 µM) inhibited the contraction induced by restoration of the extracellular Ca2+ levels after depletion of its internal stores. Similar to β-FEA, prazosin (0.1 to 30 nM) induced vasodilation in aortic rings and its concentration-effect curve was shifted to the right after treatment with ODQ. Therefore, β-FEA (1-300 µM) has vasodilatory actions in rat isolated aorta that seems to involve a role for the NO/guanylate cyclase/K+ channels pathway. It is probable that a putative α1-adrenergic receptor blocking action is involved in the vasorelaxant effect of β-FEA, although further characterization of such effect is required.