Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat

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Sarah Brøgger Kristiansen, Kristian A. Haanes, Majid Sheykhzade, Lars Edvinsson

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 ETB receptors (R) have much weaker Ca(2+)-sensitizing effect than ETA-R and that ETB-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 ETB-R upregulation.

CONCLUSION: Our data support the theory that ischemia/reperfusion may induce a phenotypical shift, which includes increased evoked ETB 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 ETA calcium handling, which has a stronger dependence on Ca(2+) release from the sarcoplasmic reticulum after I/R injury.

Original languageEnglish
JournalJournal of Molecular and Cellular Cardiology
Volume111
Pages (from-to)1-9
Number of pages9
ISSN0022-2828
DOIs
Publication statusPublished - Oct 2017

    Research areas

  • Journal Article, Calcium signaling, Endothelin signal transduction, Fura2-AM, Ischemia/reperfusion injury, Phenotypical shift, Stretch-induced tone, coronary arteries

ID: 181885213