N omega-hydroxyagmatine: a novel substance causing endothelium-dependent vasorelaxation.

Agmatine (Agm), a decarboxylated L-arginine, has been suggested to be an endogenous clonidine-displacing substance in the brain. We hypothesed that Agm enzymatically produces nitric oxide (NO) through N omega-hydroxyagmatine (OHAgm) similar to the well-known endogenous NO generation from L-arginine through N omega-hydroxy-L-arginine, because Agm possesses a guanidyl function in its molecule. OHAgm was originally synthesized from delta-aminopentanoic acid in 36% overall yield. Agm and the synthetic OHAgm were examined using rat aortic rings whether they could cause endothelium-dependent vasorelaxation or not. These substances equally elicited vasorelaxations. The relaxations were completely abolished by a NO synthase inhibitor, N omega-nitro-L-arginine methyl ester, or endothelium denudation. These results suggested that Agm and OHAgm are alternative precursors for NO generated by NOS and that OHAgm may be an endogenous substance distributable in the brain.