دورية أكاديمية
Cardioprotection by ischemic postconditioning and cyclic guanosine monophosphate-elevating agents involves cardiomyocyte nitric oxide-sensitive guanylyl cyclase.
| العنوان: | Cardioprotection by ischemic postconditioning and cyclic guanosine monophosphate-elevating agents involves cardiomyocyte nitric oxide-sensitive guanylyl cyclase. |
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| المؤلفون: | Frankenreiter, Sandra, Groneberg, Dieter, Kuret, Anna, Krieg, Thomas, Ruth, Peter, Friebe, Andreas, Lukowski, Robert |
| بيانات النشر: | //dx.doi.org/10.1093/cvr/cvy039 Cardiovasc Res Oxford University Press (OUP) |
| سنة النشر: | 2018 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Animals, Benzoates, Cyclic GMP, Disease Models, Animal, Enzyme Activators, Female, Ischemic Postconditioning, Large-Conductance Calcium-Activated Potassium Channels, Male, Mice, Knockout, Myocardial Infarction, Myocardial Reperfusion Injury, Myocytes, Cardiac, Nitric Oxide, Phosphodiesterase 5 Inhibitors, Signal Transduction, Sildenafil Citrate, Soluble Guanylyl Cyclase, Tadalafil, Tetrazoles, Thiourea, Time Factors, Up-Regulation |
| الوصف: | AIMS: It has been suggested that the nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine monophosphate (cGMP)-dependent signalling pathway affords protection against cardiac damage during acute myocardial infarction (AMI). It is, however, not clear whether the NO-GC/cGMP system confers its favourable effects through a mechanism located in cardiomyocytes (CMs). The aim of this study was to evaluate the infarct-limiting effects of the endogenous NO-GC in CMs in vivo. METHODS AND RESULTS: Ischemia/reperfusion (I/R) injury was evaluated in mice with a CM-specific deletion of NO-GC (CM NO-GC KO) and in control siblings (CM NO-GC CTR) subjected to an in vivo model of AMI. Lack of CM NO-GC resulted in a mild increase in blood pressure but did not affect basal infarct sizes after I/R. Ischemic postconditioning (iPost), administration of the phosphodiesterase-5 inhibitors sildenafil and tadalafil as well as the NO-GC activator cinaciguat significantly reduced the amount of infarction in control mice but not in CM NO-GC KO littermates. Interestingly, NS11021, an opener of the large-conductance and Ca2+-activated potassium channel (BK), an important downstream effector of cGMP/cGKI in the cardiovascular system, protects I/R-exposed hearts of CM NO-GC proficient and deficient mice. CONCLUSIONS: These findings demonstrate an important role of CM NO-GC for the cardioprotective signalling following AMI in vivo. CM NO-GC function is essential for the beneficial effects on infarct size elicited by iPost and pharmacological elevation of cGMP; however, lack of CM NO-GC does not seem to disrupt the cardioprotection mediated by the BK opener NS11021. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/273950Test |
| DOI: | 10.17863/CAM.21022 |
| الإتاحة: | https://doi.org/10.17863/CAM.21022Test https://www.repository.cam.ac.uk/handle/1810/273950Test |
| رقم الانضمام: | edsbas.C256D6F8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.21022 |
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