Conduction of feedback-mediated signal in a computational model of coupled nephrons.

Abstract

The nephron in the kidney regulates its fluid flow by several autoregulatory mechanisms. Two primary mechanisms are the myogenic response and the tubuloglomerular feedback (TGF). The myogenic response is a property of the pre-glomerular vasculature in which a rise in intravascular pressure elicits vasoconstriction that generates a compensatory increase in vascular resistance. TGF is a negative feedback response that balances glomerular filtration with tubular reabsorptive capacity. While each nephron has its own autoregulatory response, the responses of the kidney's many nephrons do not act autonomously but are instead coupled through the pre-glomerular vasculature. To better understand the conduction of these signals along the pre-glomerular arterioles and the impacts of internephron coupling on nephron flow dynamics, we developed a mathematical model of renal haemodynamics of two neighbouring nephrons that are coupled in that their afferent arterioles arise from a common cortical radial artery. Simulations were conducted to estimate internephron coupling strength, determine its dependence on vascular properties and to investigate the effect of coupling on TGF-mediated flow oscillations. Simulation results suggest that reduced gap-junctional conductances may yield stronger internephron TGF coupling and highly irregular TGF-mediated oscillations in nephron dynamics, both of which experimentally have been associated with hypertensive rats.