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Objectives: The purinergic system has not been investigated in detail following ischemia/reperfusion (I/R) injury in the heart. In the present study, we focus on both release and response to extracellular adenosine triphosphate (ATP). Pannexin (Panx) channels have been shown to be involved in ATP release from myocytes and can activate P2X1 and P2Y2 receptors on the coronary artery., Design: We applied a well-characterized I/R model in rats, with 24 hours of reperfusion. Panx expression in the myocardial tissue was measured with quantitative polymerase chain reaction (qPCR) and flow cytometry. ATP release was detected in situ using luminescence and the vascular response to nucleotides determined in a wire myograph., Results: Here, we show that Panx expression is increased after experimental myocardial I/R, leading to an increase in extracellular ATP release, which could be inhibited by probenecid. Functional studies revealed that the P2Y2 receptor-dependent contraction is reduced in the coronary artery after I/R, which might be a response to the increased ATP levels., Conclusion: We, therefore, conclude that the regulation of the arterial purinergic system minimizes coronary contractions following ischemia.

Background Acute myocardial infarction is one of the leading causes of death. It is caused by a blockage of a coronary artery leading to reduced blood flow to the myocardium and hence ischemic damage. In addition, a second wave of damage after the flow has been restored, named reperfusion injury greatly exacerbate the damage. For the latter, no medical treatment exist. In this study the aim was to characterize Ca 2+ sensitivity in coronary arteries following experimental ischemia/reperfusion injury. Methods Arteries were isolated from hearts exposed to a well-established rat ischemia/reperfusion model. Wire myograph combined with FURA2-AM measurements was applied to study the Ca 2+ dependency of the vasoconstriction. Results The results presented herein show that ET B receptors (R) have much weaker Ca 2+ -sensitizing effect than ET A -R and that ET B -R appear to be more dependent on Ca 2+ influx presumably through voltage-gated Ca 2+ channels (VGCC). In addition, we show that there is an increase in the stretch-induced tone after ischemia/reperfusion, and that this increase in tone is independent of the ET B -R upregulation. Conclusion Our data support the theory that ischemia/reperfusion may induce a phenotypical shift, which includes increased evoked ET B induced contraction in the smooth muscle cell, and also a higher basal tone development which both are dependent on Ca 2+ influx through VGCCs. This is combined with alterations in the ET A calcium handling, which has a stronger dependence on Ca 2+ release from the sarcoplasmic reticulum after I/R injury. [ABSTRACT FROM AUTHOR]