Multinephron dynamics on the renal vascular network

2013 ◽  
Vol 304 (1) ◽  
pp. F88-F102 ◽  
Author(s):  
Donald J. Marsh ◽  
Anthony S. Wexler ◽  
Alexey Brazhe ◽  
Dmitri E. Postnov ◽  
Olga V. Sosnovtseva ◽  
...  

Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each nephron to regulate blood flow and glomerular filtration rate. Both mechanisms are nonlinear, generate self-sustained oscillations, and interact as their signals converge on arteriolar smooth muscle, forming a regulatory ensemble. Ensembles may synchronize. Smooth muscle cells in the ensemble depolarize periodically, generating electrical signals that propagate along the vascular network. We developed a mathematical model of a nephron-vascular network, with 16 versions of a single nephron model containing representations of both mechanisms in the regulatory ensemble, to examine the effects of network structure on nephron synchronization. Symmetry, as a property of a network, facilitates synchronization. Nephrons received blood from a symmetric electrically conductive vascular tree. Symmetry was created by using identical nephron models at each of the 16 sites and symmetry breaking by varying nephron length. The symmetric model achieved synchronization of all elements in the network. As little as 1% variation in nephron length caused extensive desynchronization, although synchronization was maintained in small nephron clusters. In-phase synchronization predominated among nephrons separated by one or three vascular nodes and antiphase synchronization for five or seven nodes of separation. Nephron dynamics were irregular and contained low-frequency fluctuations. Results are consistent with simultaneous blood flow measurements in multiple nephrons. An interaction between electrical signals propagated through the network to cause synchronization; variation in vascular pressure at vessel bifurcations was a principal cause of desynchronization. The results suggest that the vasculature supplies blood to nephrons but also engages in robust information transfer.

1993 ◽  
Vol 264 (3) ◽  
pp. F427-F434 ◽  
Author(s):  
K. P. Yip ◽  
N. H. Holstein-Rathlou ◽  
D. J. Marsh

Modified laser-Doppler velocimetry was used to determine the number of different mechanisms regulating single-nephron blood flow. Two oscillations were identified in star vessel blood flow, one at 20-50 mHz and another at 100-200 mHz. Tubuloglomerular feedback (TGF) mediates the slower oscillation, and the faster one is probably myogenic in origin. Acute hypertension increased autospectral power in the 20-50 mHz and 100-200 mHz frequency bands to 282 +/- 50 and 248 +/- 64%, respectively, of control even though mean single-nephron blood flow was autoregulated. Mean blood flow increased 24.6 +/- 6.1% when TGF was inhibited by intratubular perfusion with furosemide, and it decreased 42.8 +/- 3.9% when TGF was saturated by tubular perfusion with artificial tubular fluid at high rates. Autospectral power in the low-frequency band decreased 50.5 +/- 9.6% during furosemide and decreased 74.9 +/- 5.9% during TGF saturation, consistent with a TGF origin of the slow oscillation. In contrast, autospectral power of the high-frequency oscillation increased 75.4 +/- 23.9% during TGF inhibition and decreased 35.8 +/- 11% when TGF was saturated, suggesting interactions between the two spontaneously oscillating components in efferent arteriole blood flow.


2009 ◽  
Vol 297 (1) ◽  
pp. F155-F162 ◽  
Author(s):  
K. L. Siu ◽  
B. Sung ◽  
W. A. Cupples ◽  
L. C. Moore ◽  
K. H. Chon

Detection of the low-frequency (LF; ∼0.01 Hz) component of renal blood flow, which is theorized to reflect the action of a third renal autoregulatory mechanism, has been difficult due to its slow dynamics. In this work, we used three different experimental approaches to detect the presence of the LF component of renal autoregulation using normotensive and spontaneously hypertensive rats (SHR), both anesthetized and unanesthetized. The first experimental approach utilized a blood pressure forcing in the form of a chirp, an oscillating perturbation with linearly increasing frequency, to elicit responses from the LF autoregulatory component in anesthetized normotensive rats. The second experimental approach involved collection and analysis of spontaneous blood flow fluctuation data from anesthetized normotensive rats and SHR to search for evidence of the LF component in the form of either amplitude or frequency modulation of the myogenic and tubuloglomerular feedback mechanisms. The third experiment used telemetric recordings of arterial pressure and renal blood flow from normotensive rats and SHR for the same purpose. Our transfer function analysis of chirp signal data yielded a resonant peak centered at 0.01 Hz that is greater than 0 dB, with the transfer function gain attenuated to lower than 0 dB at lower frequencies, which is a hallmark of autoregulation. Analysis of the data from the second experiments detected the presence of ∼0.01-Hz oscillations only with isoflurane, albeit at a weaker strength compared with telemetric recordings. With the third experimental approach, the strength of the LF component was significantly weaker in the SHR than in the normotensive rats. In summary, our detection via the amplitude modulation approach of interactions between the LF component and both tubuloglomerular feedback and the myogenic mechanism, with the LF component having an identical frequency to that of the resonant gain peak, provides evidence that 0.01-Hz oscillations may represent the third autoregulatory mechanism.


1995 ◽  
Vol 269 (4) ◽  
pp. F581-F593 ◽  
Author(s):  
R. Feldberg ◽  
M. Colding-Jorgensen ◽  
N. H. Holstein-Rathlou

The present study investigates the interaction between the tubuloglomerular feedback (TGF) response and the myogenic mechanism by use of a mathematical model. The two control mechanisms are implemented in a spatially distributed model of the rat renal juxtamedullary afferent arteriole. The model of the afferent arteriole is based on in vivo measurements of the stress-strain relation in muscle strips. Analysis of experimental data shows that the myogenic response can be modeled by a linear relation between the transmural pressure and the level of activation of the vascular smooth muscle cells. The contribution of TGF to smooth muscle activity is assumed to be a linear function of the glomerular capillary pressure. The results show that the myogenic response plays an important role in renal blood flow autoregulation. Without a myogenic response, mechanisms such as TGF that are localized in the distal segments of the microvasculature would not be able to achieve autoregulation because of passive, pressure-mediated effects in the upstream vascular segments. In addition, it is shown that a strong myogenic response may lead to both propagation and enhancement of vascular effects mediated through mechanisms located in the distal part of the afferent arteriole. An ascending myogenic response could enhance the regulatory efficiency of the TGF mechanism by increasing the open-loop gain of the system. However, such a synergistic interaction will only be observed when the two mechanisms operate on more or less separate segments of the afferent arteriole. In the case where they operate on common segments of the arteriole, the outcome of the interaction may well be antagonistic.


2009 ◽  
Vol 87 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Cam Ha T. Tran ◽  
Donald G. Welsh

Blood flow is controlled by an integrated network of resistance arteries that are coupled in series and parallel with one another. To dramatically alter tissue perfusion as required during periods of high metabolic demand, arterial networks must dilate in a coordinated manner. Gap junctions facilitate arterial coordination by enabling electrical stimuli to conduct among endothelial and (or) smooth muscle cells. The goal of this review was to provide an introduction to the field of vascular communication, the process of intercellular conduction, and the manner in which key properties influence charge flow. After a brief historical introduction, we establish the idea that electrical stimuli conduct differentially among neighbouring endothelial and smooth muscle cells. Highlighting recent studies that have synergistically combined computational and experimental approaches, this perspective explores how specific structural, electrical, and gap junctional properties enable electrical phenomenon to conduct differentially. To close, the concept of differential communication is functionally integrated into a mechanistic understanding of blood flow control.


2011 ◽  
Vol 300 (2) ◽  
pp. F319-F329 ◽  
Author(s):  
Niels-Henrik Holstein-Rathlou ◽  
Olga V. Sosnovtseva ◽  
Alexey N. Pavlov ◽  
William A. Cupples ◽  
Charlotte Mehlin Sorensen ◽  
...  

Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50–100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic techniques for extracting the desired data and for examining them for evidence of nephron synchronization. Synchronized TGF oscillations were detected in pairs or triplets of nephrons. The amplitude and the frequency of the oscillations changed with time, as did the patterns of synchronization. Synchronization may take place among nephrons not immediately adjacent on the surface of the kidney.


Ultrasound ◽  
2021 ◽  
pp. 1742271X2110224
Author(s):  
Sonja Brennan ◽  
David Watson ◽  
Michal Schneider ◽  
Donna Rudd ◽  
Yogavijayan Kandasamy

Introduction The study objectives were to develop standard charts for fetal renal artery blood flow to define normal ranges and to assess the reliability of the measurements. Methods This prospective, longitudinal study reviewed 72 low-risk singleton pregnancies who had serial ultrasound examinations. Pulse wave Doppler was used to obtain the resistivity and pulsatility indices of the fetal renal arteries. Standard charts of the fetal renal arteries were created using mixed effects modelling and the intra- and interobserver reliability for the renal blood flow measurements was analysed. Results Standard charts of the normal ranges of the renal artery resistive index (RI) and pulsatility index (PI) of the fetal renal arteries were created. The 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles were calculated. The intraclass correlation coefficient was acceptable for intraobserver reliability (RI = 0.66, PI = 0.88) and poor for interobserver reliability (RI = 0.11, PI = −0.56). Conclusions These novel charts demonstrate the change of the fetal renal artery blood flow during pregnancy. These may be used in clinical practice to detect variations from these normal ranges and be useful in future studies of kidney function projection.


Neurosurgery ◽  
2002 ◽  
Vol 50 (5) ◽  
pp. 996-1005 ◽  
Author(s):  
Randolph S. Marshall ◽  
Ronald M. Lazar ◽  
William L. Young ◽  
Robert A. Solomon ◽  
Shailendra Joshi ◽  
...  

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