In vivo vascular rarefaction and hypertension induced by dexamethasone are related to phosphatase PTP1B activation not endothelial metabolic changes
| Autor: | Jeannette Vasquez-Vivar, Naiara A. Herrera, Allison Kahlke, Sandra Lia do Amaral, Francine Duchatsch |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Medical College of Wisconsin |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Microvascular Rarefaction Bradykinin Glucocorticoid receptor Biochemistry Dexamethasone Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance In vivo Physiology (medical) Internal medicine polycyclic compounds medicine Animals Endothelial dysfunction Endothelial Cells medicine.disease VEGF Phosphoric Monoester Hydrolases Rats 030104 developmental biology Endocrinology chemistry Hypertension 030217 neurology & neurosurgery Glucocorticoid hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Free Radic Biol Med |
| Popis: | Made available in DSpace on 2020-12-12T01:12:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-20 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) National Institutes of Health Glucocorticoids have important anti-inflammatory and immunomodulatory activities. Dexamethasone (Dex), a synthetic glucocorticoid, induces insulin resistance, hyperglycemia, and hypertension. The hypertensive mechanisms of Dex are not well understood. Previously, we showed that exercise training prior to Dex treatment significantly decreases blood vessel loss and hypertension in rats. In this study, we examined whether the salutary effects of exercise are associated with an enhanced metabolic profile. Analysis of the NAD and ATP content in the tibialis anterior muscle of trained and non-trained animals indicated that exercise increases both NAD and ATP; however, Dex treatment had no effect on any of the experimental groups. Likewise, Dex did not change NAD and ATP in cultured endothelial cells following 24 h and 48 h of incubation with high concentrations. Reduced VEGF-stimulated NO production, however, was verified in endothelial cultured cells. Reduced NO was not associated with changes in survival or the BH4 to BH2 ratio. Moreover, Dex had no effect on bradykinin- or shear-stress-stimulated NO production, indicating that VEGF-stimulated eNOS phosphorylation is a target of Dex's effects. The PTP1B inhibitor increased NO in Dex-treated cells in a dose-dependent fashion, an effect that was replicated by the glucocorticoid receptor inhibitor, RU486. In combination, these results indicate that Dex-induced endothelial dysfunction is mediated by glucocorticoid receptor and PTP1B activation. Moreover, since exercise reduces the expression of PTP1B and normalized insulin resistance in aging rats, our findings indicate that exercise training by reducing PTP1B activity counteracts Dex-induced hypertension in vivo. Joint Graduate Program in Physiological Sciences PIPGCF UFSCar/UNESP, Rodovia Washington Luiz, São Carlos/SP Department of Physical Education São Paulo State University School of Sciences, Av. Eng. Luiz Edmundo Carrijo Coube Department of Biophysics Redox Biology Program Medical College of Wisconsin Joint Graduate Program in Physiological Sciences PIPGCF UFSCar/UNESP, Rodovia Washington Luiz, São Carlos/SP Department of Physical Education São Paulo State University School of Sciences, Av. Eng. Luiz Edmundo Carrijo Coube FAPESP: #2017/00509-1 FAPESP: 2016/12532-5 FAPESP: 2017/14405-3 FAPESP: 2018/06998-7 National Institutes of Health: R01 NS081936 |
| Databáze: | OpenAIRE |
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