Zhuge 2017 Redox Biol

Zhuge Z, Paulo LL, Jahandideh A, Brandão MCR, Athayde-Filho PF, Lundberg JO, Braga VA, Carlström M, Montenegro MF (2017) Synthesis and characterization of a novel organic nitrate NDHP: Role of xanthine oxidoreductase-mediated nitric oxide formation. Redox Biol 13:163-9.

» PMID: 28578274

Zhuge Z, Paulo LL, Jahandideh A, Brandao MCR, Athayde-Filho PF, Lundberg JO, Braga VA, Carlstroem M, Montenegro MF (2017) Redox Biol

Abstract: In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved. • Keywords: Nitrate, Nitric oxide, Nitrite, Organic nitrates, Tolerance, Xanthine oxidoreductase • Bioblast editor: Kandolf G • O2k-Network Lab: SE Stockholm Weitzberg E

Labels: MiParea: Respiration, Comparative MiP;environmental MiP 

Organism: Mouse, Rat  Tissue;cell: Endothelial;epithelial;mesothelial cell 

HRR: Oxygraph-2k 

Labels, 2017-08