Regulation of renal perfusion and oxygenation in sepsis-induced acute kidney injury

• Applicant: Dr. Erdmann Seeliger, since 2/2015
• Subject Area: Anatomy and Physiology ; Nephrology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152203169

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).

• DFG Programme: Research Units
• Subproject of: FOR 1368: Hemodynamic Mechanisms of Acute Kidney Injury
• Ehemaliger Antragsteller: Karen Arakelyan, until 2/2015