A Multicellular Vascular Model of the Renal Myogenic Response

Abstract

Abstract:The myogenic response is a key autoregulatory mechanism in the mammalian kidney. Triggered by blood pressure perturbations, it is well established that the myogenic response is initiated in the renal afferent arteriole and mediated by alterations in muscle tone and vascular diameter that counterbalance hemodynamic perturbations. The entire process involves several subcellular, cellular, and vascular mechanisms whose interactions remain poorly understood. Here, we model and investigate the myogenic response of a multicellular segment of an afferent arteriole. Extending existing work, we focus on providing an accurate-but still computationally tractable-representation of the coupling among the involved levels. For individual muscle cells, we include detailed Ca 2+ signaling, transmembrane transport of ions, kinetics of myosin light chain phosphorylation, and contraction mechanics. Intercellular interactions are mediated by gap junctions between muscle or endothelial cells. Additional interactions are mediated by hemodynamics. Simulations of time-independent pressure changes reveal regular vasoresponses throughout the model segment and stabilization of a physiological range of blood pressures (80-180 mmHg) in agreement with other modeling and experimental studies that assess steady autoregulation. Simulations of time-dependent perturbations reveal irregular vasoresponses and complex dynamics that may contribute to the complexity of dynamic autoregulation observed in vivo. The ability of the developed model to represent the myogenic response in a multiscale and realistic fashion, under feasible computational load, suggests that it can be incorporated as a key component into larger models of integrated renal hemodynamic regulation.

Numerical Modeling and Simulation of Blood Flow in a Rat Kidney: Coupling of the Myogenic Response and the Vascular Structure

“…[25]. Furthermore, experiments deep inside the kidney examining a complex vascular structure and flow may affect the proper working condition of the blood vessels and therefore the accuracy of the data, as preparation procedures to access the interior of kidneys and AAs in isolation may alter the AAs behavior [31].…”

“…The myogenic response model acted at each AA to constrict the vessel [30][31][32], demonstrating the regulation of pressure at individual subsystems [13,27] as…”

“…However, a wider range of interlobular pressure P CRA would be obtained in this study with the use of detailed vascular structures, which did not exclude the small vascular structures such as interlobular arteries (Figure 1a). Furthermore, the AAs were designated as the only vessel capable of constriction [30][31][32]. Thus, the glomerular pressure P 0 = 6.7 kPa [33][34][35] was assumed more suitable as a pressure criterion to accurately represent the response of the AA to P GC changes.…”

Non-linear dynamics of morphogenetic renal branching and Bifurcation analysis of chaotic patterns in autoregulation mechanisms

“…We incorporate the myogenic functions of a broad number of smooth muscle cells. 6 let the QAA and QEA signify the distribution of blood in the afferent and efferent arterioles models, accordingly. A fraction of the blood supply is separated from the circulation in the glomerulus, which is the primary section of the nephron and where filtration takes place.…”