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Arterial redox signalling in the control of bood pressure under inflammatory conditions
Under inflammatory conditions, the haem-containing indoleamine 2,3-dioxygenase 1 is expressed in arterial endothelial cells. In the presence of hydrogen peroxide, the endothelial enzyme generates 1O2 and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophan-derived hydroperoxide acts in vivo as a signalling molecule, inducing arterial relaxation and decreasing blood pressure; this activity is dependent on Cys42 of protein kinase G1α. Our findings demonstrate a pathophysiological role for singlet oxygen in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions.