FG 1368

Principal Investigators: Erdmann Seeliger, Bert Flemming and Pontus Persson

Renal outer medullary hypoxia plays a pivotal role in acute kidney injury (AKI). Reduced bioavailability of vasodilatory nitric oxide (NO) directly promotes hypoperfusion and hypoxia; in addition, it disinhibits the synthesis of vasoconstrictive 20-hydroxyeicosatetraenoic acid (20-HETE). According to a new paradigm of hypoxic vasodilation, hemoglobin (Hb) is a regulated nitrite reductase. Hb reduces nitrite to NO as it deoxygenates, thus causing vasodilation in hypoxic regions only. We hypothesise that, in the setting of AKI, nitrite causes renal medullary vasodilation in hypoxic regions. As nitrite is reduced to NO in hypoxic areas only, it may constitute a reasonably specific measure in preventing AKI. We have established methods for integrative in vivo studies on regulation of kidney hemodynamics and oxygenation in rats, and applied these methods to study contrast medium induced nephropathy (CIN). Here, we study the role of nitrite-derived NO for hemodynamics and oxygenation in rat models of CIN and of renal ischemia/reperfusion (I/R) injury (a standardized model of the Research Unit).