β-Resorcylidene aminoguanidine (RAG) dilates coronary arteries in an endothelium-independent manner.
BACKGROUND
β-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.


METHODS
Isolated 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.


RESULTS
RAG 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.


CONCLUSIONS
RAG is a strong vasodilator that exerts its effect via endothelium-independent mechanisms.
Department of Haemostatic Disorders, Medical University of Lodz, Łódź, Poland; Department of Cardiosurgery, Polish Mother's Memorial Hospital - Research Institute, Łódź, Poland. Electronic address: kazmierczak_piotr@yahoo.com.
Piotr A
PA
Kazmierczak
Department of Haemostatic Disorders, Medical University of Lodz, Łódź, Poland; Department of Medicine, Baylor College of Medicine, Houston, USA.
Marcin P
MP
Dobaczewski
Department of Haemostatic Disorders, Medical University of Lodz, Łódź, Poland.
Tomasz
T
Przygodzki
Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Bratislava, Slovakia.
Jozef
J
Carsky
Department of Haemostatic Disorders, Medical University of Lodz, Łódź, Poland.
Cezary
C
Watala
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D006146:Guanidines; C115168:resorcylidene aminoguanidine
Coronary arteries; Endothelium-dependent and endothelium-independent vasodilatation; Langendorff perfusion; β-Resorcylidene aminoguanidine