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.
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Authors | Angel Luis García-Villalón, Nuria Fernández, Luis Monge, Godofredo Diéguez |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 660
Issue 2-3
Pg. 394-401
(Jun 25 2011)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 21513710
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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