Endothelin receptor mediated Ca²⁺ signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat.

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 Ca²⁺ 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 Ca²⁺ dependency of the vasoconstriction. RESULTS:The results presented herein show that ET_B receptors (R) have much weaker Ca²⁺-sensitizing effect than ET_A-R and that ET_B-R appear to be more dependent on Ca²⁺ influx presumably through voltage-gated Ca²⁺ 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 Ca²⁺ influx through VGCCs. This is combined with alterations in the ET_A calcium handling, which has a stronger dependence on Ca²⁺ release from the sarcoplasmic reticulum after I/R injury.

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