title: Coronary response to diadenosine pentaphosphate after ischaemia-reperfusion in the isolated rat heart.
abstract: OBJECTIVE
  Diadenosine polyphosphates are vasoactive mediators that may be released from platelet granules and which may be present at higher concentrations during coronary ischaemia-reperfusion. The objective of this study was to analyse their effects in such conditions.
  
  
  RESULTS
  Rat hearts were perfused in a Langendorff preparation and the response to diadenosine pentaphosphate (Ap5A, 10(-7)-10(-5) M) was recorded. In control hearts, Ap5A produced a small, transient coronary vasoconstriction followed by marked vasodilatation, as well as a reduction in the left ventricular developed pressure dP/dt and heart rate, both at the basal coronary resting tone or after pre-contracting coronary arteries with 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha (U46619). After ischaemia-reperfusion, the vasoconstriction in response to Ap5A was augmented and vasodilatation diminished, both in hearts with basal or increased vascular tone. The pyridoxal derivative P(2) purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 3 x 10(-6) M), inhibited this vasoconstriction, while the antagonist of purinergic P(2Y) receptors, Reactive Blue 2 (2 x 10(-6) M), inhibited the vasodilatation, both before and after ischaemia-reperfusion. The antagonist of nitric oxide synthesis N-omega-nitro-L- arginine methyl ester (L-NAME, 10(-4) M) did not modify the response to Ap5A, whereas the cyclooxygenase inhibitor, meclofenamate (2 x 10(-6) M), reduced contraction and increased the relaxation in response to Ap5A after ischaemia-reperfusion but not under control conditions.
  
  
  CONCLUSIONS
  Ischaemia-reperfusion reduces the vasodilatory response to Ap5A and increases the vasoconstriction provoked due to a reduced influence of purinergic P(2Y) receptors and/or to the production of vasoconstrictor prostanoids.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 2, 28029 Madrid, Spain. angeluis.villalon@uam.es
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: Luis
authors.initials: L
authors.lastname: Monge
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández
authors.forename: Adely
authors.initials: A
authors.lastname: Salcedo
authors.forename: Raúl
authors.initials: R
authors.lastname: Narváez-Sánchez
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; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D015226:Dinucleoside Phosphates; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D011732:Pyridoxal Phosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019331:NG-Nitroarginine Methyl Ester