Complex I dysfunction and tolerance to nitroglycerin: an approach based on mitochondrial-targeted antioxidants.

Nitroglycerin (GTN) tolerance was induced in vivo (rats) and in vitro (rat and human vessels). Electrochemical detection revealed that the incubation dose of GTN (5x10(-6) mol/L) did not release NO or modify O(2) consumption when administered acutely. However, development of tolerance produced a decrease in both mitochondrial O(2) consumption and the K(m) for O(2) in animal and human vessels and endothelial cells in a noncompetitive action.

Endothelial nitric oxide synthase regulates T cell receptor signaling at the immunological synapse.

The role of nitric oxide (NO) in T cells remains controversial, and the origin and localization of endogenous NO and whether it regulates lymphocyte activation are unclear. We show here that, within minutes of binding to antigen, T cells produce NO via endothelial nitric oxide synthase (eNOS). This process required increased intracellular Ca2+ and phosphoinositide3-kinase activity.