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This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/141    most recent expphysiol.2007.038588v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mitchell, J. A. Articles by Harrington, L. S. Search for Related Content PubMed PubMed Citation Articles by Mitchell, J. A. Articles by Harrington, L. S. Related Collections Symposia Papers

¹ Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK

Abstract

The endothelium lines the luminal surface of every blood vessel, allowing it contact with circulating blood elements, as well as the underlying vascular smooth muscle layer. In healthy vessels, the endothelium expresses constitutive forms of nitric oxide synthase (NOSIII) and cyclo-oxygenase (COX-1), which produce the vasoactive hormones NO and prostacyclin, respectively. Both NO and prostacyclin relax blood vessels and inhibit platelet activation. The actions of prostacyclin are mediated by cell surface prostacyclin (IP) receptors and/or intracellular peroxisome proliferator-activated receptors (PPAR)β. The actions of NO are mediated predominately by activation of intracellular guanylyl cyclase, leading to the formation of cGMP. In platelets, the actions of NO and prostacyclin are synergistic, but in vessels their actions are additive. In diseased vessels, inducible forms of NOS (NOSII) and cyclo-oxygeanse (COX-2) are expressed in vascular smooth muscle, resulting in the release of large amounts of NO, prostacyclin and prostaglandin E₂. The relative contribution of NOSII and COX-2 to vascular inflammation is still debated, but is likely to result in both protective and damaging responses. The relative contribution of constitutive forms of NOS and COX, as well as interactions between IP, PPARβ and guanylyl cyclase pathways in vessels and platelets, is discussed.

(Received 11 June 2007; accepted after revision 21 September 2007; first published online 26 October 2007)
Corresponding author J. A. Mitchell: Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK. Email: j.a.mitchell{at}ic.ac.uk