Contrast media (CM) induced acute kidney injury (CM-AKI) is the third leading cause for acute renal failure. We only incompletely understand the development of CM-AKI, which most certainly involves hypoxia of the outer medulla. A number of characteristics of CM have been proposed to be responsible for CM-AKI. The probably most relevant characteristics of CM regarding the pathophysiology of CM-AKI have only recently attracted attention: The rheological properties of CM, namely their viscosity and the potential of CM to directly constrict vasa recta. Latter are highly specialised vessels supplying the region at risk for CM-AKI. Here we report of the direct vasoconstrictor action of CM on isolated vasa recta, and on the alterations in renal microcirculation after giving CM. Using microdissection techniques, single descending vasa recta were isolated from rats and perfused using a set of concentric pipettes. Digital videomicroscopy was used for measurements of luminal diameter. For microcirculation measurements, local pO2 and laser Doppler flux were measured. Also, a microviscosimeter was developed to measure viscosity in minute samples. The viscosity of certain CM increases tubular fluid viscosity 50-fold leading to an increase in resistance and renal interstitial pressure, and finally to a reduction of renal medullary flow and thus a decrease in of the glomerular filtration rate. These findings prompted a Swedish registry study, which included data on over 57,000 patients, which supports the proposed pathomechanisms. Supported by FOR 1368 (Hemodynamic mechanisms of AKI)