Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation
| Autor: | Hua Cai, Jonathan J. Langberg, Samuel C. Dudley, Josiah N. Wilcox, David G. Harrison, Andreas Goette, Fernando Mera, Zongming Li, Kristian Feterik, Clegg Honeycutt |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Swine medicine.medical_treatment Blotting Western Down-Regulation Catheter ablation Nitric Oxide Nitric oxide Electrocardiography chemistry.chemical_compound Physiology (medical) Internal medicine Atrial Fibrillation Plasminogen Activator Inhibitor 1 medicine Animals Heart Atria Atrium (heart) Fibrillation biology business.industry Cardiac Pacing Artificial Thrombosis Atrial fibrillation medicine.disease Immunohistochemistry Myocardial Contraction Up-Regulation Stroke Nitric oxide synthase Disease Models Animal Endocrinology medicine.anatomical_structure chemistry Plasminogen activator inhibitor-1 cardiovascular system biology.protein Female Nitric Oxide Synthase medicine.symptom Cardiology and Cardiovascular Medicine business Endocardium |
| Zdroj: | Circulation. 106:2854-2858 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background— In the arterial endothelium, laminar flow and cyclical stretch induce expression of NO synthase (NOS). We hypothesized that atrial fibrillation (AF) causes a downregulation of atrial endocardial NOS expression and NO · production. Because NO · has antithrombotic properties, this may contribute to thromboembolism in AF. Methods and Results— In pigs, AF was produced with rapid atrial pacing at 600 bpm for 1 week, whereas controls had atrial pacing at 100 bpm. All animals had catheter ablation of the AV junction and ventricular pacing at 100 bpm. NO · production from freshly isolated tissue was measured by a NO · -specific microelectrode. Left atrial basal and stimulated NO · production was decreased in AF by 73% and 71% ( P · and was increased in the left atrium by 1.8-fold in AF ( P · concentration was decreased in the left atrial appendage, although NOS expression was not affected. Neither NOS concentration, NO · levels, nor PAI-1 expression were altered in the aortas or right atria of animals with AF. Conclusions— AF is associated with a marked decrease in endocardial NOS expression and NO · bioavailability and an increase in PAI-1 expression in the left atrium. These data suggest that organized atrial contraction is needed to maintain normal endocardial expression of NOS. It is likely that loss of this antithrombotic enzyme contributes to the thromboembolic phenomena commonly observed in AF. |
| Databáze: | OpenAIRE |
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