Abstract:
:The identification of nitric oxide ((*)NO) as an endogenously produced free radical mediator of endothelial-dependent relaxation and host defense has fundamentally changed concepts of cell signal transduction. Ligand-receptor oriented paradigms of cell signaling were originally centered on the concept of a high affinity and specific interaction between a ligand and its receptor, resulting in the activation of secondary signaling events such as gene expression or modulation of catalytic protein function. While (*)NO ligation of the heme iron of soluble guanylate cyclase is consistent with this perspective, the readily diffusible and broadly reactive (*)NO is increasingly appreciated to react with a vast array of target molecules that mediate paracrine vasodilator actions, inhibition of thrombosis and neointimal proliferation, and both pro- and antiinflammatory signaling reactions that are not affected by inhibitors of soluble guanylate cyclase. There is an expanding array of functionally significant "off target" collateral reactions mediated by (*)NO that are guanylate cyclase-independent and rather are dictated by anatomic distribution and the formation of secondary (*)NO-derived species. These reactions are a critical element of redox-regulated signaling and are addressed herein in the context of the oxidation of unsaturated fatty acids to vascular and inflammatory signaling mediators. Because of their abundance and the intrinsic reactivity of unsaturated lipid intermediates and eicosanoid metabolism enzymes with (*)NO and other oxides of nitrogen, lipid signaling mechanisms are a significant target for regulation by (*)NO in the vascular compartment. This convergence of (*)NO and lipid signaling pathways thus adds another level of regulation to physiological responses such as vasodilation, thrombosis, and inflammation. Herein, interactions between (*)NO and lipid signaling events are placed in the context of cardiovascular regulation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Rudolph V,Freeman BAdoi
10.1161/CIRCRESAHA.109.202077subject
Has Abstractpub_date
2009-09-11 00:00:00pages
511-22issue
6eissn
0009-7330issn
1524-4571pii
105/6/511journal_volume
105pub_type
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