Free radical biology & medicine, 2011-04, Vol.50 (7), p.765-776
2011
Details
- Autor(en) / Beteiligte
- Titel
- Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders
- Ist Teil von
- Free radical biology & medicine, 2011-04, Vol.50 (7), p.765-776
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits platelet aggregation. Chronically, eNOS has a major role in the regulation of blood pressure and prevention of atherosclerosis by decreasing leukocyte adhesion and smooth muscle proliferation. However, a disturbed vascular redox balance results in eNOS damage and uncoupling of oxygen activation from l-arginine conversion. Uncoupled eNOS monomerizes and generates reactive oxygen species (ROS) rather than NO. Indeed, eNOS uncoupling has been suggested as one of the main pathomechanisms in a broad range of cardiovascular and pulmonary disorders such as atherosclerosis, ventricular remodeling, and pulmonary hypertension. Therefore, modulating uncoupled eNOS, in particular eNOS-dependent ROS generation, is an attractive therapeutic approach to preventing and/or treating cardiopulmonary disorders, including protective effects during cardiothoracic surgery. This review provides a comprehensive overview of the pathogenetic role of uncoupled eNOS in both cardiovascular and pulmonary disorders. In addition, the related therapeutic possibilities such as supplementation with the eNOS substrate l-arginine, volatile NO, and direct NO donors as well as eNOS modulators such as the eNOS cofactor tetrahydrobiopterin and folic acid are discussed in detail.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0891-5849eISSN: 1873-4596DOI: 10.1016/j.freeradbiomed.2010.12.018Titel-ID: cdi_crossref_primary_10_1016_j_freeradbiomed_2010_12_018
- Format
- –
- Schlagworte
- adhesion, Arginine - metabolism, Arginine - pharmacology, Arginine - therapeutic use, atherosclerosis, Atherosclerosis - drug therapy, Atherosclerosis - metabolism, Atherosclerosis - physiopathology, Biopterins - analogs & derivatives, Biopterins - pharmacology, Biopterins - therapeutic use, blood pressure, Blood Pressure - drug effects, blood vessels, Cardiac Surgical Procedures - adverse effects, Cardioprotection, Cell Adhesion - drug effects, citrulline, endothelial nitric oxide synthase, Endothelium, Vascular - drug effects, Endothelium, Vascular - metabolism, Endothelium, Vascular - physiopathology, eNOS modulators, eNOS uncoupling, folic acid, Folic Acid - pharmacology, Folic Acid - therapeutic use, Free radicals, Humans, hypertension, Hypertension, Pulmonary - drug therapy, Hypertension, Pulmonary - metabolism, Hypertension, Pulmonary - physiopathology, leukocytes, nitric oxide, Nitric Oxide - metabolism, Nitric Oxide - pharmacology, Nitric Oxide - therapeutic use, Nitric Oxide Donors - pharmacology, Nitric Oxide Donors - therapeutic use, Nitric Oxide Synthase Type III - metabolism, Oxidation-Reduction, oxygen, Oxygen - metabolism, platelet aggregation, protective effect, reactive oxygen species, Reactive Oxygen Species - adverse effects, Reactive Oxygen Species - metabolism, respiratory tract diseases, smooth muscle, Superoxide, surgery, Tetrahydrobiopterin, Vasodilation - drug effects, Ventricular Remodeling - drug effects