Differential roles of nitric oxide synthase isozymes in cardiotoxicity and mortality following chronic doxorubicin treatment in mice
| العنوان: | Differential roles of nitric oxide synthase isozymes in cardiotoxicity and mortality following chronic doxorubicin treatment in mice |
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| المؤلفون: | Friedrich Brunner, Albrecht Schmidt, Ute Gödtel-Armbrust, Leszek Wojnowski, Shiwei Deng, Annegret Metzger, Gerd Hasenfuss, Anke Kruger, Tiandong Yan |
| المصدر: | Naunyn-Schmiedeberg's Archives of Pharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Genetically modified mouse, medicine.medical_specialty, Heart Diseases, Nitric Oxide Synthase Type III, Nitric Oxide Synthase Type II, Mice, Transgenic, Nitric Oxide Synthase Type I, 030204 cardiovascular system & hematology, Pharmacology, Biology, Nitric Oxide, Nitric oxide, Contractility, Mice, 03 medical and health sciences, chemistry.chemical_compound, Biomedicine, Neurosciences, Pharmacology/Toxicology, 0302 clinical medicine, Enos, Internal medicine, polycyclic compounds, medicine, Animals, Mortality, Gene knockout, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Cardiotoxicity, Antibiotics, Antineoplastic, Nitric oxide synthase, General Medicine, biology.organism_classification, Myocardial Contraction, 3. Good health, Mice, Inbred C57BL, Survival Rate, Disease Models, Animal, Endocrinology, chemistry, Doxorubicin, biology.protein, Original Article |
| الوصف: | The roles of individual nitric oxide synthases (NOS) in anthracycline-related cardiotoxicity are not completely understood. We investigated the effects of a chronic treatment with doxorubicin (DOX) on knockouts of the individual NOS isozymes and on transgenic mice with myocardial overexpression of eNOS. Fractional shortening (FS) was reduced in untreated homozygous nNOS and iNOS knockouts as well as in eNOS transgenics. DOX-induced FS decrease in wild-type mice was attenuated only in eNOS knockouts, which were found to overexpress nNOS. No worsening of contractility was observed in DOX-treated eNOS transgenics and iNOS knockouts. Although the surviving DOX-treated nNOS knockouts exhibited no further impairment in contractility, most (70%) animals died within 7 weeks after treatment onset. In comparison to untreated wild-type hearts, the nitric oxide (NO) level was lower in hearts from DOX-treated wild-type mice and in all three untreated knockouts. DOX treatment had no effect on NO in the knockouts. These data indicate differential roles of the individual NOS in DOX-induced cardiotoxicity. Protection against DOX effects conferred by eNOS deletion may be mediated by a compensatory overexpression of nNOS. NOS inhibition-based prevention of anthracycline-induced cardiotoxicity should be eNOS-selective, simultaneously avoiding inhibiting nNOS. peerReviewed |
| وصف الملف: | application/pdf |
| تدمد: | 1432-1912 0028-1298 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e5ca782f24e39154786d1775dbf12fdTest https://doi.org/10.1007/s00210-009-0407-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e5ca782f24e39154786d1775dbf12fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321912 00281298 |
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