Theoretical assessment of renal autoregulatory mechanisms

A mathematical model of renal hemodynamics was used to assess the individual contributions of the tubuloglomerular feedback (TGF) mechanism and the myogenic response to glomerular filtration rate regulation in the rat kidney. The model represents an afferent arteriole segment, glomerular filtration, and a short loop of Henle. The afferent arteriole model exhibits myogenic response, which is activated by hydrostatic pressure variations to induce changes in membrane potential and vascular muscle tone. The tubule model predicts tubular fluid and Cl(-) transport. Macula densa Cl(-) concentration is sensed as the signal for TGF, which acts to constrict or dilate the afferent arteriole. With this configuration, the model afferent arteriole maintains stable glomerular filtration rate within a physiologic range of perfusion pressure (80-180 mmHg). The contribution of TGF to overall autoregulation is significant only within a narrow band of perfusion pressure values (80-110 mmHg). Model simulations of ramp-like perfusion pressure perturbations agree well with findings by Flemming et al. (Flemming B, Arenz N, Seeliger E, Wronski T, Steer K, Persson PB. J Am Soc Nephrol 12: 2253-2262, 2001), which indicate that changes in vascular conductance are markedly sensitive to pressure velocity. That asymmetric response is attributed to the rate-dependent kinetics of the myogenic mechanism. Moreover, simulations of renal autoregulation in diabetes mellitus predict that, due to the impairment of the voltage-gated Ca(2+) channels of the afferent arteriole smooth muscle cells, the perfusion pressure range in which single-nephron glomerular filtration rate remains stable is reduced by ~70% and that TGF gain is reduced by nearly 40%, consistent with experimental findings.