Original research articleβ-Resorcylidene aminoguanidine (RAG) dilates coronary arteries in an endothelium-independent manner

Backgroundβ-Resorcylidene aminoguanidine (RAG), a highly reactive derivative of aminoguanidine, possesses antithrombotic activity which involves the activation of the vascular COX-2/PGI2 pathway. This endothelium-dependent effect suggests that RAG may demonstrate vasomotor activity in arterial vessels. The aim of the present study was to investigate a possible vasoactive action of RAG in coronary arteries of rat heart.MethodsIsolated rat hearts were perfused in the Langendorff model. To investigate the dose dependency of the effect of RAG on coronary flow, the hearts were perfused with RAG at increasing concentrations. Mechanisms of RAG-mediated vasodilation were subsequently tested using selective inhibitors of the endothelium-dependent and endothelium-independent mechanisms responsible for regulation of vascular tone.ResultsRAG dilated coronary arteries at concentrations above 10−5 mol/l. Inhibition of the endothelium-dependent mechanism of vasodilation by NG-nitro-l-arginine methyl ester, indomethacin and aminobenzotriazole did not affect RAG-mediated vasodilation. Other compounds also had no impact on the vasodilating effect of RAG: the NO-dependent guanylate cyclase inhibitor - 1H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one, the cAMP-dependent protein kinase inhibitor - PKAi, and the K+ channel blockers - glibenclamide, tetraethylammonium, charybdotoxin, and apamin.ConclusionsRAG is a strong vasodilator that exerts its effect via endothelium-independent mechanisms.