Feedback-mediated dynamics in a model of coupled nephrons with compliant thick ascending limbs

Bowen, Matthew L.; Wen, Amy; Layton, Harold E.

doi:10.1016/j.mbs.2011.02.004

Cited by 7 publications

(9 citation statements)

References 37 publications

(71 reference statements)

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“…Combining several copies of the present model, which incorporates both TGF and the myogenic response, may shed new light on the importance of internephron coupling on the dynamic behavior of the system. The stability of the resulting system can be investigated via the bifurcation analysis used in the present study, following the approach of [31,47]. …”

Section: Discussionmentioning

confidence: 99%

Bifurcation study of blood flow control in the kidney

Versypt

Makrides

Arciero

et al. 2015

Mathematical Biosciences

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Renal blood flow is maintained within a narrow window by a set of intrinsic autoregulatory mechanisms. Here, a mathematical model of renal hemodynamics control in the rat kidney is used to understand the interactions between two major renal autoregulatory mechanisms: the myogenic response and tubuloglomerular feedback. A bifurcation analysis of the model equations is performed to assess the effects of the delay and sensitivity of the feedback system and the time constants governing the response of vessel diameter and smooth muscle tone. The results of the bifurcation analysis are verified using numerical simulations of the full nonlinear model. Both the analytical and numerical results predict the generation of limit cycle oscillations under certain physiologically relevant conditions, as observed in vivo.

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Section: Discussionmentioning

confidence: 99%

Bifurcation study of blood flow control in the kidney

Versypt

Makrides

Arciero

et al. 2015

Mathematical Biosciences

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“…This review concentrates on the changes in preglomerular vascular resistance responsible for regulation of RBF and glomerular perfusion. The reader is referred to recent reviews of renal autoregulation (286, 748,933,934) and of mathematical modeling of renal autoregulatory mechanisms (179,228,395,541,628,805,877,973,1023,1350,1614).…”

Section: Renal Autoregulatory Mechanismsmentioning

confidence: 99%

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

381

383

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Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

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“…Thus, tubular wall compliance is expected to have a significant impact on the response time and dynamic behaviors of TGF. TGF models that represent compliant tubular walls have been developed [49, 54]. Model results suggest that tubular compliance reduces the stability of the TGF system.…”

Section: Tubuloglomerular Feedbackmentioning

confidence: 99%

“…TGF models previously discussed have been extended to networks of two or more nephrons, e.g., Refs. [54, 55, 47, 33, 34, 35]. …”

Section: Tubuloglomerular Feedbackmentioning

confidence: 99%

Mathematical modeling of renal hemodynamics in physiology and pathophysiology

Sgouralis¹

2015

Mathematical Biosciences

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In addition to the excretion of metabolic waste and toxin, the kidney plays an indispensable role in regulating the balance of water, electrolyte, acid-base, and blood pressure. For the kidney to maintain proper functions, hemodynamic control is crucial. In this review, we describe representative mathematical models that have been developed to better understand the kidney's autoregulatory processes. We consider mathematical models that simulate glomerular filtration, and renal blood flow regulation by means of the myogenic response and tubuloglomerular feedback. We discuss the extent to which these modeling efforts have expanded the understanding of renal functions in health and disease.

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Feedback-mediated dynamics in a model of coupled nephrons with compliant thick ascending limbs

Cited by 7 publications

References 37 publications

Bifurcation study of blood flow control in the kidney

Bifurcation study of blood flow control in the kidney

Renal Autoregulation in Health and Disease

Mathematical modeling of renal hemodynamics in physiology and pathophysiology

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