Non-adrenergic inhibition at prejunctional sites by agmatine of purinergic vasoconstriction in rabbit saphenous artery.

We investigated the effects of agmatine, clonidine, xylazine and moxonidine on the purinergic vasoconstriction induced by electrical stimulation in the rabbit isolated saphenous artery without endothelium. Transmural electrical stimulations induced reproducible responses in the arterial preparations, which were abolished by tetrodotoxin at 0.1 microM or pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS, 30 microM), but were not affected by 1 microM prazosin. Clonidine, xylazine and moxonidine induced transient and concentration-independent vasoconstriction, with threshold concentrations of 1, 3 and 30 microM, respectively. Agmatine, in contrast, did not produce any vascular response even at 1 mM. Lower concentrations of clonidine, xylazine and moxonidine (0.01-0.3 microM) concentration-dependently decreased vasoconstrictor responses to electrical stimulation, whereas agmatine (0.1-1 mM) induced an inhibitory followed by a facilitatory effect on electrically evoked responses. Agmatine, clonidine and moxonidine but not xylazine significantly enhanced the vasoconstriction elicited by 1 mM ATP. The concentration-response curve for NA was shifted to the left slightly by 1 mM agmatine, but not affected by 0.3 microM of other three agonists. Phenoxybenzamine did not affect the vasoconstrictive responses to 1mM ATP and to electrical stimulations, but abolished those to NA. Agmatine at 1mM evoked only an inhibitory effect on electrical stimulation-induced vasoconstriction in the preparation pretreated with phenoxybenzamine, and the inhibitory action was enhanced to 38.6% from the control value (without treatment with phenoxybenzamine) of 22.5%. The non-imidazoline compound xylazine at 0.3 microM lost its inhibitory effect on the neurogenic vasoconstriction in the presence of phenoxybenzamine. In conclusion, agmatine produces a biphasic effect on the purinergic vasoconstriction induced by sympathetic nerve stimulation in the rabbit isolated saphenous artery. The monophasic inhibition of agmatine in the artery treated with phenoxybenzamine is due to an alpha-adrenoceptor-independent mechanism at prejunctional sites, and the potentiation effect of agmatine is mainly dependent on its enhancement of vasoconstriction at postjunctional sites.