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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.
AuthorsAngel Luis García-Villalón, Nuria Fernández, Luis Monge, Godofredo Diéguez
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 660 Issue 2-3 Pg. 394-401 (Jun 25 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21513710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Androstadienes
  • Dinucleoside Phosphates
  • Endothelin-1
  • Estrenes
  • Indoles
  • Isoquinolines
  • Maleimides
  • Pyrrolidinones
  • Sulfonamides
  • Triazines
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • diadenosine tetraphosphate
  • Cibacron Blue F 3GA
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Isatin
  • bisindolylmaleimide I
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Glyburide
  • NG-Nitroarginine Methyl Ester
  • Wortmannin
Topics
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (pharmacology)
  • Androstadienes (pharmacology)
  • Animals
  • Coronary Vessels (drug effects, physiopathology)
  • Dinucleoside Phosphates (pharmacology)
  • Endothelin-1 (pharmacology)
  • Estrenes (pharmacology)
  • Glyburide (pharmacology)
  • Heart (drug effects, physiopathology)
  • In Vitro Techniques
  • Indoles (pharmacology)
  • Isatin (pharmacology)
  • Isoquinolines (pharmacology)
  • Male
  • Maleimides (pharmacology)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Perfusion
  • Pyrrolidinones (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (physiopathology)
  • Rest
  • Sulfonamides (pharmacology)
  • Triazines (pharmacology)
  • Vasoconstriction (drug effects)
  • Wortmannin

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