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Processes 2018, 6(7), 89;

A Multicellular Vascular Model of the Renal Myogenic Response

Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210, USA
Department of Mathematics, University of Arizona, Tucson, AZ 85719, USA
National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, TN 37996, USA
Departments of Mathematics, Biomedical Engineering, and Medicine, Duke University, Durham, NC 27708, USA
Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
Author to whom correspondence should be addressed.
Received: 5 June 2018 / Revised: 29 June 2018 / Accepted: 5 July 2018 / Published: 17 July 2018
(This article belongs to the Special Issue Systems Biomedicine)
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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 Ca2+ 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. View Full-Text
Keywords: nonlinear model; smooth muscle; gap junctions; microcirculation; kidney; hemodynamics nonlinear model; smooth muscle; gap junctions; microcirculation; kidney; hemodynamics

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ciocanel, M.-V.; Stepien, T.L.; Sgouralis, I.; Layton, A.T. A Multicellular Vascular Model of the Renal Myogenic Response. Processes 2018, 6, 89.

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