AGMATINE, AN ENDOGENOUS MODULATOR OF NORADRENERGIC NEUROTRANSMISSION IN THE RAT TAIL ARTERY

1 We investigated the vascular effects of agmatine (decarboxylated arg inine), an endogenous ligand for alpha(2)-adrenoceptors and non-adreno ceptor imidazoline (I-) receptors, present in endothelium, smooth musc le and plasma, using the rat tail artery as a model. 2 While by itself agmatine (10 nM-1 mM) was without effect on isolated arterial rings, at the highest concentration used (1 mM) it slightly increased EC(50) values for contractions elicited respectively by the alpha(1)- and alp ha(2)-adrenoceptor agonists methoxamine and clonidine. 3 Agmatine (0.0 3-1 mM) produced a concentration-dependent transient inhibition of the contractions induced by transmural nerve stimulation (TNS; 200 mA, 0. 2 ms: 1 Hz, 10 s). This effect was abolished by the alpha(2)-adrenocep tor antagonists, rawolscine and idazoxan. 4 In the presence of rawolsc ine or idazoxan, agmatine produced a concentration-dependent delayed f acilitation of TNS-induced contractions, which was prevented by cocain e. 5 Neither inhibitory nor potentiating actions were produced by agma tine on contractions induced by noradrenaline (NA) administration. 6 A gmatine did not directly affect [H-3]-NA uptake in bovine cultured chr omaffin cells. 7 Agmatine can regulate vascular function by two opposi ng actions at sympathetic nerve terminals, with different latencies: a transient inhibition of NA release mediated by prejunctional alpha(2) -adrenoceptors and a cocaine-sensitive delayed facilitation the mechan ism of which is undetermined at present. 8 The results reveal the exis tence of a novel endogenous amine modulating NA release in the perivas cular sympathetic terminals.