P56: Aldehyde dehydrogenase plays an important role in nitrite-mediated vasorelaxation during hypoxic conditions

Abstract

Background Several experimental studies have reported that the conversion of nitrite to nitric oxide (NO) may occur by a family of (hemo) proteins that exhibit ‘nitrite reductase’ activity, including globins, xanthine oxidoreductase and endothelial NO synthase. Moreover, recent studies have demonstrated aldehyde dehydrogenase (ALDH) to be an important source of nitrite-derived NO in rat blood vessels and heart, respectively. However to date, no prior research has been undertaken to investigate the effects of ALDH inhibition on nitrite-mediated vasodilatation during normoxic and hypoxic conditions. Aim To determine the role of ALDH in nitrite-mediated vasorelaxation, a dose response curve to sodium nitrite was investigated in isolated rat thoracic arota. Briefly, the vessels were subjected to normoxic or hypoxic conditions and a dose response curve to sodium nitrite was then constructed in the presence and absence of ALDH inhibitor, cyanamide, or ALDH substrate, propionaldehyde. Results No significant difference was observed between the degree of nitrite-induced relaxation in the presence and absence of cyanamide under normoxic conditions. In contrast, hypoxia enhanced nitrite-induced relaxation, but following ALDH inhibition with cyanamide, there was a significant rightward shift of the concentration response curves to sodium nitrite. Similar results were also obtained using the ALDH substrate, propionaldehyde. Conclusion These results suggest that ALDH plays an important role in the nitrite-mediated vasorelaxation in isolated rat thoracic aorta during hypoxic conditions. Disclosure Supported by a research grant from British Heart Foundation.