COX-mediated endothelium-dependent contractions: from the past to recent discoveries.
Endothelial cells release various substances to control the tone of the underlying vascular smooth muscle. Nitric oxide (NO) is the best defined endothelium-derived relaxing factor (EDRF). Endothelial cells can also increase vascular tone by releasing endothelium-derived contracting factors (EDCF). The over-production of EDCF contributes to the endothelial dysfunctions which accompanies various vascular diseases. The present review summarizes and discusses the mechanisms leading to the release of EDCFs derived from the metabolism of arachidonic acid. This release can be triggered by agonists such as acetylcholine, adenosine nucleotides or by stretch. All these stimuli are able to induce calcium influx into the endothelial cells, an effect which can be mimicked by calcium ionophores. The augmentation in intracellular calcium ion concentration initiates the release of EDCF. Downstream processes include activation of phospholipase A(2) (PLA(2)), cyclooxygenases (COX) and the production of reactive oxygen species (ROS) and vasoconstrictor prostanoids (endoperoxides, prostacyclin, thromboxane A(2) and other prostaglandins) which subsequently diffuse to, and activate thromboxane-prostanoid (TP) receptors on the vascular smooth muscle cells leading to contraction.
Wong
Michael Sze-Ka
MS
Department of Pharmacology and Pharmacy, University of Hong Kong, China.
Vanhoutte
Paul Michel
PM
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D054467:Phospholipases A2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism*
D011453:Prostaglandins; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2