title: Coronary response to diadenosine tetraphosphate after ischemia-reperfusion in the isolated rat heart.
abstract: Diadenosine tetraphosphate (AP4A) is a vasoactive mediator that may be released from platelet granules and that may reach higher plasma concentrations during coronary ischemia-reperfusion. The objective of this study was to analyze its coronary effects in such conditions. To this, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap4A (10(-7)-10(-5) M) was recorded. In control hearts, Ap4A produced concentration-dependent vasodilatation both at the basal coronary resting tone and after precontracting coronary vasculature with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2α (U46619), and this vasodilatation was reduced by reactive blue 2 (2×10(-6) M), glibenclamide (10(-5) M), H89 (10(-6) M), U73122 (5×10(-6) M) and endothelin-1 (10(-9) M), but not by L-NAME (10(-4) M), isatin (10(-4) M), GF109203x (5×10(-7) M), or wortmannin (5×10(-7) M). After ischemia-reperfusion, the vasodilatation to Ap4A diminished, both in hearts with basal or increased vascular tone, and in this case the relaxation to Ap4A was not modified by reactive blue 2, L-NAME, glibenclamide, isatin, H89, GF109203x or wortmannin, although it was reduced by U73122 and endothelin-1. UTP produced coronary relaxation that was also reduced after ischemia-reperfusion. These results suggest that the coronary relaxation to Ap4A is reduced after ischemia-reperfusion, and that this reduction may be due to impaired effects of KATP channels and to reduced response of purinergic P2Y receptors.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain. angeluis.villalon@uam.es
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández
authors.forename: Luis
authors.initials: L
authors.lastname: Monge
authors.forename: Godofredo
authors.initials: G
authors.lastname: Diéguez
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007510:Isatin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012146:Rest; D013449:Sulfonamides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D015226:Dinucleoside Phosphates; D019332:Endothelin-1; D004963:Estrenes; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D011760:Pyrrolidinones; D013449:Sulfonamides; D014227:Triazines; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C020733:diadenosine tetraphosphate; C012842:Cibacron Blue F 3GA; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007510:Isatin; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D000077191:Wortmannin