Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase
| Autor: | Brent A. French, Michael A. Moskowitz, Zequan Yang, Ali Hafezi-Moghadam, Dao-Shan Chui, Jean-Christophe Plumier, Kennard L. Thomas, Victor E. Laubach, Michela C. Rebsamen, Tommaso Simoncini, Florian P. Limbourg, Alyson Prorock, Klaus Ley, James K. Liao, Chung-Ming Hsieh |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Cardiotonic Agents Nitric Oxide Synthase Type III Endothelium Nitric Oxide Synthase Type II In Vitro Techniques Pharmacology Dexamethasone Muscle Smooth Vascular General Biochemistry Genetics and Molecular Biology Article Potassium Chloride Nitric oxide Mice chemistry.chemical_compound Glucocorticoid receptor Adrenal Cortex Hormones Enos Internal medicine medicine Animals Humans Protein kinase B Aorta Cells Cultured biology General Medicine medicine.disease biology.organism_classification Enzyme Activation Nitric oxide synthase NG-Nitroarginine Methyl Ester Endocrinology medicine.anatomical_structure chemistry biology.protein Endothelium Vascular Nitric Oxide Synthase Reperfusion injury Muscle Contraction |
| Popis: | Corticosteroids have been shown to exert beneficial effects in the treatment of acute myocardial infarction, but the precise mechanisms underlying their protective effects are unknown. Here we show that high-dose corticosteroids exert cardiovascular protection through a novel mechanism involving the rapid, non-transcriptional activation of endothelial nitric oxide synthase (eNOS). Binding of corticosteroids to the glucocorticoid receptor (GR) stimulated phosphatidylinositol 3-kinase and protein kinase Akt, leading to eNOS activation and nitric oxide dependent vasorelaxation. Acute administration of pharmacological concentrations of corticosteroids in mice led to decreased vascular inflammation and reduced myocardial infarct size following ischemia and reperfusion injury. These beneficial effects of corticosteroids were abolished by GR antagonists or eNOS inhibitors in wild-type mice and were completely absent in eNOS-deficient (Nos3(-/-)) mice. The rapid activation of eNOS by the non-nuclear actions of GR, therefore, represents an important cardiovascular protective effect of acute high-dose corticosteroid therapy. |
| Databáze: | OpenAIRE |
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