Sarah Brøgger Kristiansen1, Kristian A Haanes2, Majid Sheykhzade3, Lars Edvinsson4. 1. Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet-Glostrup, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. 2. Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet-Glostrup, Denmark. Electronic address: kristian.agmund.haanes@regionh.dk. 3. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. 4. Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet-Glostrup, Denmark.
Abstract
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 ETB receptors (R) have much weaker Ca2+-sensitizing effect than ETA-R and that ETB-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 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 Ca2+ influx through VGCCs. This is combined with alterations in the ETA calcium handling, which has a stronger dependence on Ca2+ release from the sarcoplasmic reticulum after I/R injury.
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 ratischemia/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 ETB receptors (R) have much weaker Ca2+-sensitizing effect than ETA-R and that ETB-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 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 Ca2+ influx through VGCCs. This is combined with alterations in the ETA calcium handling, which has a stronger dependence on Ca2+ release from the sarcoplasmic reticulum after I/R injury.
Authors: Simon T Christensen; Sara E Johansson; Aneta Radziwon-Balicka; Karin Warfvinge; Kristian A Haanes; Lars Edvinsson Journal: PLoS One Date: 2019-04-12 Impact factor: 3.240
Authors: Mei Yuan; Xiao-Wen Meng; Jiao Ma; Hong Liu; Shao-Yong Song; Qing-Cai Chen; Hua-Yue Liu; Juan Zhang; Nan Song; Fu-Hai Ji; Ke Peng Journal: Drug Des Devel Ther Date: 2019-09-02 Impact factor: 4.162