Purinergic Receptor Activation Protects Glomerular Microvasculature from Increased Mechanical Stress in Angiotensin II-Induced Hypertension: A Modeling Study

Figures

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  Figure 3. Model algorithm. Resistance to filtration, Rf, and viscosity, µ, are iteratively calculated for each capillary segment until both quantities converge. After convergence is reached, SNGFR is calculated and compared to a target SNGFR value, and k is altered to better fit the model to the target SNGFR. Once all quantities have converged, the model is fit to the data, and individual glomerular capillary filtration rates (CSGFRs) and mechanical stresses can be assessed. In Table 1, we perform a dimensional analysis of the relevant model variables.

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  Figure 1. Average mechanical stresses exerted on the glomerular capillary network. (A) Shear stress on the endothelial cells is elevated with blockade of the P2X1 receptor, consistent with increased flow under these conditions. (B) Circumferential hoop stress is elevated in all treatment groups, independent of P2X1 blockade. * p < 0.05; ** p < 0.005; *** p < 0.0001; NS, not significant, as assessed by Welch’s T-test.

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  Figure 2. Localized shear stresses exerted on each glomerular capillary. (A) Shear stress values are mapped on their corresponding capillaries in the glomerular capillary network. Each segment of the network represents a capillary segment, with nodes representative of points of coalescence and/or bifurcation. Arrows indicate flow direction of the model. AA: afferent arteriole, EA: efferent arteriole. Diagram not drawn to scale. (B) Individual capillary segment shear stresses are plotted for the NF449 treatment groups against their respective control (AngII or Sham), demonstrating significant differences between capillaries of each case and the same capillaries between cases.