Hypoxia and vasa recta function

• Applicants: Professor Andreas Patzak, Ph.D.; Professor Dr. Pontus Börje Persson; Mauricio Sendeski, Ph.D.
• Subject Area: Anatomy and Physiology ; Nephrology
• Term: from 2011 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152203169

Contrast media induced nephropathy (CIN) is the third most common cause of hospital-acquired AKI1. The steady increase of coronary interventions underscores the demand for an effective prevention and therapy of CIN. In accordance to the unifying hypothesis of this Research Unit, we propose that reduced blood flow and oxygen tension to the outer renal medulla is a key feature causing CIN. Juxtamedullary nephrons are responsible for the blood supply of the medulla. We, therefore, investigate the contribution of afferent (AA) and efferent arterioles (EA), and the distal tubule (Macula densa) to contrast media (CM) induced impairment of renal hemodynamics. CM may act directly on AA, EA, and tubules. Damage of endothelial and smooth muscle cells and the release of vasoactive substances from tubules may add to perturb local hemodynamics. Acute experiments will be performed in the isolated AA and EA. The double perfused juxtaglomerular apparatus will serve for investigating tubuloglomerular interactions. CM-effects on arteriolar tone and reactivity, and underlying cellular mechanisms will be investigated with special attention to ROS, NO, Ang II, and adenosine, which are crucial for renal medullary blood flow control and the tubuloglomerular feedback. Further we investigate cytotoxicity of CM on the endothelium and the protective action of adrenomedullin on endothelial cells in renal vessels.

• DFG Programme: Research Units
• Subproject of: FOR 1368: Hemodynamic Mechanisms of Acute Kidney Injury
• International Connection: Sweden
• Major Instrumentation: hypoxstation
• Instrumentation Group: 3060 Atemgas- und Blutgas-Analysatoren
• Participating Person: Dr. Mattias Carlström