The Distribution of Blood in Renal Glomerular Capillaries Is a New Physiological Parameter, Which Is Affected by Diabetes and ACE‐inhibition (2019)

Dysregulation of capillary blood flow seems associated with a number of diseases, but the majority of measurements of capillary flow distributions have been performed in brain or muscle capillary beds. From other organs, e.g. the kidney, there is a lack of empirical data on capillary blood distributions and lack of knowledge about the relationships between capillary blood distributions and disease states. This study aims to provide measurements of red blood cell (rbc) velocities in renal glomerular capillaries in vivo. The study further aims to investigate if and how the distribution of rbc velocities in renal glomerular capillaries is affected by STZ-induced diabetes and by ACE-inhibition in age-induced chronic kidney disease (CKD) in Münich Wistar Frömter rats. Glomerular capillary rbc velocities were recorded by 2-photon in-vivo microscopy using single capillary linescans after plasma labeling with 500kD-dextran-SetAu-647. In total, we recorded blood velocities in 2582 capillaries (c) distributed on 253 glomeruli (g) and 38 rats (r). Two experiments were performed: In the Diabetes-experiment 3 groups of rats were studied: Control (C) (r=10, g=63, c=558)), Diabetic (D) (STZ.injection 7 days prior to microscopy) (r=11, g=91, c=965) and Acute hyperglycemic (AH)(glucose injections during microscopy)(r=8, g=52, c=491). In the CKD study a control group (CKD) (r=5, g= 18, c = 156) and a Lisinopril-treated group (LIS) (10 weeks of Lisinopril in drinking water)(r=4, g=29, c=412) were studied. The glomerular capillary rbc velocities (mean±SD, mm/s,) in the 5 groups were: C: 3.74±1.48, D: 3.11±1.05, AH: 3.18±1.40, CKD 3.15±1.30 and LIS: 2.92±0.85 The variability of capillary rbc velocities in a glomerulus was proportional to the mean velocity in the glomerulus (p<0.001). Using a mixed-model analysis, the overall distribution of rbc velocities in within the glomerular capillary beds did not follow a Gaussian distribution (p<0.001), but rather followed a log-normal distribution. The probabilities that the variability in rbc velocity within a glomerulus is less in diabetic than untreated control rats and in acutely hyperglycemic rats, were found to be 0.94 and 0.99 respectively. The probability that Lisinopril induces less variability in the blood velocities within a glomerulus was > 0.999. This study shows, that the distribution of blood in the glomerular capillary bed is a new parameter in renal physiology, which is changed independently from total glomerular blood velocity. The implications of these findings are, that the surface area available for filtration in the kidney is not an anatomically fixed constant, but is a dynamic variable depending on intraglomerular distribution of blood. Support or Funding Information Danish Medical Research Council (4004-00149), Oticon-foundation, Aarhus University “MEMBRANES” Recorded rbc velocities in glomerular capillaries This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.