Project 2: Hypoxia and vasa recta function
According to the unifying hypothesis, disturbed vascular function together with reduced renal perfusion is a key for the development of AKI. The inner part of the outer medulla, supplied by vasa recta, is an area at risk for hypoxic damage. We assume that vasa recta dysfunction is of paramount importance for the reduced medullary perfusion in AKI, and hypothesize that adenosine - which increases 5-fold during renal ischemia - plays an important role for regulation of vasa recta. We will use an in vitro model of hypoxia/re-oxygenation. The contribution of adenosine receptors, transporters and of ectonucleotidases to the effects of adenosine will be investigated. We employ knock out animals for A1, A2A, and A2B receptors and pharmacological approaches. Moreover, light is shed onto the interaction of adenosine with the angiotensin system and eicosanoids. The potential role of recently discovered angiotensin like peptides, as well as 20-HETE and EETs, on vasa recta function in hypoxia/reoxygenation will be assessed. Kidney medullary slices and isolated, perfused vasa recta will be used to access vessel function in conditions of graded hypoxia and re-oxygenation. Also, the cross talk between vasa recta and tubules will be assessed in medullary slices. To this end, we apply videomicroscopy combined with differential interference contrast and two-photon confocal fluorescence microscopy for studying vasa recta and tubular function.
*Dr. Sendeski left the institution in December 2015.