Cyclooxygenase-2 and nitric oxide.
Nitric oxide (NO) is a simple but pluripotent molecule that is mainly released from vascular endothelial cells where it is formed intracellularly by nitric oxide synthase from L-arginine in response to several stimuli, including shear stress or muscarinic receptor stimulation. NO stimulates guanylyl cyclase to form cyclic guanosine monophosphate, which results in relaxation and vasodilatation of vascular smooth muscle cells (VSMCs). In addition, NO prevents adhesion and aggregation of platelets, and it possesses anti-inflammatory, antiproliferative, and antimigratory effects on leukocytes, endothelial cells, and VSMCs, thus offering protection from atherosclerosis. Dysfunction of the vascular endothelium has been documented in most conditions that promote or are associated with atherosclerosis and is characterized by a reduced bioavailability of NO. The healthy endothelium prevents adhesion and migration of leukocytes, proliferation of VSMCs, and platelet adhesion and aggregation. Maintaining the balance of blood flow and thrombus formation is also a major task of the vascular endothelium. It has been shown that both NO and prostacyclin, a cyclooxygenase-derived relaxing factor, inhibit activation of platelets and regulate vasomotion. Reduced NO and prostacyclin levels can result in endothelial dysfunction, which is recognized as the first step in the atherogenic process. It is of note that chronic inflammation conditions, such as rheumatoid arthritis, are associated with endothelial dysfunction. The reduced NO bioavailability may therefore explain the increased risk for cardiovascular events in patients with chronic low-grade inflammation, such as rheumatoid arthritis and osteoarthritis. Thus, this article provides an overview of the impact of inflammation and anti-inflammatory treatment with cyclooxygenase inhibitors on endothelial function.
Hermann
Matthias
M
Department of Cardiology, University Hospital Zürich, Zürich, Switzerland. mhermann@gmx.de
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D009569:Nitric Oxide; D051546:Cyclooxygenase 2