Modeling Autoregulation of the Afferent Arteriole of the Rat Kidney

Abstract

One of the key autoregulatory mechanisms that control blood flow in the kidney is the myogenic response. Subject to increased pressure, the renal afferent arteriole responds with an increase in muscle tone and a decrease in diameter. To investigate the myogenic response of an afferent arteriole segment of the rat kidney, we extend a mathematical model of an afferent arteriole cell. For each cell, we include detailed Ca2+ signaling, transmembrane transport of major ions, the kinetics of myosin light chain phosphorylation, as well as cellular contraction and wall mechanics. To model an afferent arteriole segment, a number of cell models are connected in series by gap junctions, which link the cytoplasm of neighboring cells. Blood flow through the afferent arteriole is modeled using Poiseuille flow. Simulation of an inflow pressure up-step leads to a decrease in the diameter for the proximal part of the vessel (vasoconstriction) and to an increase in proximal vessel diameter (vasodilation) for an inflow pressure down-step. Through its myogenic response, the afferent arteriole segment model yields approximately stable outflow pressure for a physiological range of inflow pressures (100–160 mmHg), consistent with experimental observations. The present model can be incorporated as a key component into models of integrated renal hemodynamic regulation.