Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress
| Autor: | Rabelo, L.A., Todiras, M., Nunes-Souza, V., Qadri, F., Szijártó, I.A., Gollasch, M., Penninger, J.M., Bader, M., Santos, R.A., Alenina, N. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Physiology lcsh:Medicine Blood Pressure Vasodilation Urine 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry Vascular Medicine Antioxidants Renin-Angiotensin System Lipid peroxidation Mice chemistry.chemical_compound 0302 clinical medicine Enos Medicine and Health Sciences lcsh:Science Aorta Multidisciplinary Neurochemistry Animal Models Enzymes Body Fluids Chemistry Dismutases medicine.anatomical_structure Physical Sciences Female Angiotensin-Converting Enzyme 2 Anatomy Neurochemicals Oxidation-Reduction hormones hormone substitutes and hormone antagonists Research Article medicine.medical_specialty Nitric Oxide Synthase Type III Endothelium Mouse Models Peptidyl-Dipeptidase A Biology Nitric Oxide Research and Analysis Methods Nitric oxide Superoxide dismutase 03 medical and health sciences Model Organisms Internal medicine medicine Animals RNA Messenger Nitrites Superoxide Dismutase lcsh:R Chemical Compounds Biology and Life Sciences Proteins Cell Biology biology.organism_classification Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology chemistry Cardiovascular and Metabolic Diseases Cardiovascular Anatomy Enzymology biology.protein Blood Vessels lcsh:Q Endothelium Vascular Lipid Peroxidation Gene Deletion Homeostasis Oxidative stress Neuroscience |
| Zdroj: | PLoS ONE, Vol 11, Iss 4, p e0150255 (2016) PLOS ONE PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance. |
| Databáze: | OpenAIRE |
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