Artikel
Impact of C-type natriuretic peptide on myocardial ischemia/reperfusion injury in mice
Die Bedeutung des C-Typ Natriuretischen Peptides für die Pathologie nach myokardialer Ischemie/Reperfusion in der Maus
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Veröffentlicht: | 8. August 2006 |
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Background: C-type natriuretic peptide (CNP) has been implicated in the regulation of coronary blood flow and the reduction of ischemia/reperfusion (I/R)-induced infarct size in isolated perfused Langendorff rat hearts via interaction with natriuretic peptide receptor C. We examined the effect of cardiomyocyte-specific overexpressed CNP vs. minipump-infused CNP in an in vivo model of I/R injury in mice.
Methods and Results: Overexpression of CNP in cardiomyocytes was confirmed by RNase Protection Assay (RPA) and Radioimmunoassay. CNP mRNA was overexpressed in the transgenic atria and ventricles, but could not be detected in other organs. CNP peptide concentration was significantly increased in TG mice atria (TG: 17.8±4.0 pg/ml vs. WT: 3.7±0.7 pg/ml, p<0.05) and ventricles (TG: 10.7±1.3 pg/ml vs. WT: 0.2±0.1 pg/ml, p<0.001).
Three to five-month-old male TG mice and their WT littermates were subjected to 1-hour global myocardial ischemia and 23 hours reperfusion. Another set of WT mice received CNP (0.25 microgramm g/h) or saline through minipumps 15 to 20 hours before I/R insult until the end of the experiment. The area at risk (AAR) was evaluated by tryptan blue and infarct area (IA) by TTC, then digitally measured using SigmaScan. AAR over left ventricle was similar in all groups (TG: 43±3%, WT: 45±2%, n=9; WT received CNP: 42±5%, WT received saline: 48±5%, n=6). The myocardial infarct size was expressed as a percentage of IA over total AAR. There was no significant difference in infarct size (TG: 68±8% vs. WT: 69±7%, n=9) between TG and WT. Also in the second set of animals, infusion of CNP did not alter the infarct size (CNP: 89±3% vs. saline: 91±1%, n=6).
Conclusion: Overexpression of CNP in cardiomyocytes or infusion of CNP in mice cannot reduce myocardial infarct size induced by I/R, in contrast to the formerly described beneficial effect of CNP infusion in Langendorff rat hearts.