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Endogenous Imidazoline Receptor Ligands Relax Rat Aorta by an Endothelium‐Dependent Mechanism

2003; Wiley; Volume: 1009; Issue: 1 Linguagem: Inglês

10.1196/annals.1304.027

1749-6632

Ian F. Musgrave, Andrea van der Zypp, MATHEW GRIGG, Colin J. Barrow,

Neurotransmitter Receptor Influence on Behavior

A bstract : Agmatine and harmane have been proposed as endogenous ligands of imidazoline receptors. Agmatine has been reported to activate nitric oxide synthetase (NOS) in endothelial cells, so we sought to determine if agmatine or harmane and an analogue of harmane, propyl harmane, produced vasodilatation through an endothelium‐dependent mechanism. The experiments were performed in endothelium‐denuded and intact rat aortic rings preconstricted with phenylephrine (0.1 m M). Agmatine (0.3–1000 m M), harmane, and propyl harmane (0.3–100 m M) relaxed endothelium‐intact rings in a concentration‐dependent manner. Removal of endothelium inhibited the relaxant effect of agmatine, harmane, and propyl harmane. The NOS inhibitor L‐NIO (100 m M) inhibited the relaxant effect of agmatine and harmane. The I 1 ‐receptor antagonist AGN (100 m M) partly inhibited the effect of harmane but not that of agmatine. These results suggest that the endogenous imidazoline ligands are capable of stimulating NOS largely by an I 1 ‐receptor‐independent mechanism.