Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat
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Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat. / Kristiansen, Sarah Brøgger; Haanes, Kristian A.; Sheykhzade, Majid; Edvinsson, Lars.
In: Journal of Molecular and Cellular Cardiology, Vol. 111, 10.2017, p. 1-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat
AU - Kristiansen, Sarah Brøgger
AU - Haanes, Kristian A.
AU - Sheykhzade, Majid
AU - Edvinsson, Lars
N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Journal Article
KW - Calcium signaling
KW - Endothelin signal transduction
KW - Fura2-AM
KW - Ischemia/reperfusion injury
KW - Phenotypical shift
KW - Stretch-induced tone
KW - coronary arteries
U2 - 10.1016/j.yjmcc.2017.07.013
DO - 10.1016/j.yjmcc.2017.07.013
M3 - Journal article
C2 - 28757442
VL - 111
SP - 1
EP - 9
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
ER -
ID: 181885213