Biomedical subjects

N H Holstein-Rathlou

Publications and source records attributed to N H Holstein-Rathlou.

At least 55 records · Page 3Linked to original sources

PubMed1995

Analysis of interaction between TGF and the myogenic response in renal blood flow autoregulation.

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.

Animals↗

PubMed1994

A dynamic model of renal blood flow autoregulation.

To test whether a mathematical model combining dynamic models of the tubuloglomerular feedback (TGF) mechanism and the myogenic mechanism was sufficient to explain dynamic autoregulation of renal blood flow, we compared model simulations with experimental data. To assess the dynamic characteristics of renal autoregulation, a broad band perturbation of the arterial pressure was employed in both the simulations and the experiments. Renal blood flow and tubular pressure were used as response variables in the comparison. To better approximate the situation in vivo where a large number of individual nephrons act in parallel, each simulation was performed with 125 parallel versions of the model. The key parameters of the 125 versions of the model were chosen randomly within the physiological range. None of the constituent models, i.e., the TGF and the myogenic, could alone reproduce the experimental observations. However, in combination they reproduced most of hte features of the various transfer functions calculated from the experimental data. The major discrepancy was the presence of a bimodal distribution of the admittance phase in the simulations. This is not consistent with most of the experimental data, which shows a unimodal curve for the admittance phase. The ability of the model to reproduce the experimental data supports the hypothesis that dynamic autoregulation of renal blood flow is due to the combined action of TGF and the myogenic response.

Animals↗

PubMed1994

Glomerular filtration rate and segmental tubular function in the early phase after transplantation/uninephrectomy in recipients and their living-related kidney donors.

1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria. 2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P < 0.05). In the donors glomerular filtration rate had increased to 59 ml/min by day 5 (P < 0.01) and was unchanged at day 54. 3. In the recipients lithium clearance was unchanged at day 5 and had increased to 23 ml/min at day 54 (P < 0.01). In the donors the lithium clearance had increased by day 5 (P < 0.01). 4. In the recipients the absolute proximal fluid reabsorption rate was about 36 ml/min throughout the study period. In the donors the absolute proximal fluid reabsorption rate had increased to 42 ml/min by day 5 (P < 0.05) and increased further to 44 ml/min by day 54 (P < 0.01). 5. In the recipients sodium clearance increased from 0.54 ml/min to 2.10 ml/min at day 54 (P < 0.01). In the donors it increased from 0.64 ml/min to 0.99 ml/min at day 54 (P < 0.05). 6. Donor-recipient comparison showed that at day 54 there was no significant difference with regard to glomerular filtration rate, lithium clearance, absolute and fractional proximal fluid reabsorption rate and absolute distal sodium reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Lack of evidence for low-dimensional chaos in heart rate variability.

INTRODUCTION: The term chaos is used to describe erratic or apparently random time-dependent behavior in deterministic systems. It has been suggested that the variability observed in the normal heart rate may be due to chaos, but this question has not been settled. METHODS AND RESULTS: Heart rate variability was assessed by recordings of consecutive RR intervals in ten healthy subjects using ambulatory ECG. All recordings were performed with the subjects at rest in the supine position. To test for the presence of nonlinearities and/or chaotic dynamics, ten surrogate time series were constructed from each experimental dataset. The surrogate data were tailored to have the same linear dynamics and the same amplitude distribution as the original data. Experimental and surrogate data were then compared using various nonlinear measures. Power spectral analysis of the RR intervals showed a 1/f pattern. The correlation dimension differed only slightly between the experimental and the surrogate data, indicating that linear correlations, and not a "strange" attractor, are the major determinants of the calculated correlation dimension. A test for nonlinear predictability showed coherent nonlinear dynamic structure in the experimental data, but the prediction error as a function of the prediction length increased at a slower rate than characteristic of a low-dimensional chaotic system. CONCLUSION: There is no evidence for low-dimensional chaos in the time series of RR intervals from healthy human subjects. However, nonlinear determinism is present in the data, and various mechanisms that could generate such determinism are discussed.

Adolescent↗

PubMed1994

On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption.

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ+dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in Pgc and Pprox and thus leaves delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining delta P and therefore GFR during conditions where tubular flow rate is increased.

Absorption↗

PubMed1994

Detection of interactions between myogenic and TGF mechanisms using nonlinear analysis.

Previous studies using linear techniques have provided valuable insights into the dynamic characteristics of whole kidney autoregulation and have led to the general conclusion that the myogenic mechanism and tubuloglomerular feedback (TGF) are highly nonlinear control mechanisms. To explore further the dynamic nature of these nonlinear autoregulatory mechanisms, we introduce the technique of nonlinear modeling using Volterra-Wiener kernels. In the past several years, use of Volterra-Wiener kernels for nonlinear approximation has been most notably applied to neurophysiology. Recent advances in algorithms for computation of the kernels have made this technique more attractive for the study of the dynamics of nonlinear physiological systems, such as the system mediating renal autoregulation. In this study, the general theory and requirements for using this technique are discussed. The feasibility of using the technique on whole kidney pressure and flow data is examined, and a basis for using the Volterra-Wiener kernels to detect interactions between physiological control mechanisms is established. As a result of this method, we have identified the presence of interactions between the oscillating components of the myogenic and the TGF mechanisms at the level of the whole kidney blood flow in normotensive rats. An interaction between these oscillatory components had previously been demonstrated only at the single-nephron level.

Animals↗

PubMed1994

Active lithium transport by rat renal proximal tubule: a micropuncture study.

We tested the hypothesis that proximal tubular Li+ reabsorption is due to passive transport. Clearances of [14C]inulin (CIn) and Li+ (CLi), proximal transepithelial electrical potential difference (PD), and tubular fluid-to-plasma Li+ concentration ratios [(TF/P)Li] were measured in anesthetized rats before and after induction of osmotic mannitol diuresis. Late proximal (TF/P)Li was measured after acute intravenous LiCl administration and after addition of LiCl to the diet for 2 days. Glomerular filtration rate (CIn) decreased, whereas CNa and CLi increased during osmotic diuresis. Control early proximal PD was -0.6 mV (lumen negative); late proximal PD (PDLP) was 1.1 mV (lumen positive). PDLP decreased by 1.5 mV to -0.4 mV (lumen negative) after mannitol infusion. Late proximal (TF/P)Li was 1.01 after oral Li+, 1.16 after intravenous Li+ (P < 0.01), and 1.00 during osmotic diuresis. It is concluded that proximal Li+ transfer is distinct from that of Na+, closely parallels proximal water transfer, and involves an active transport mechanism independent of the PD. The data suggest that acute elevation of plasma Li+ concentration may activate a delayed Li+ transport pathway in the proximal convoluted tubule.

Anesthesia↗

PubMed1994

Renal blood flow regulation and arterial pressure fluctuations: a case study in nonlinear dynamics.

The arterial blood pressure, a physiological variable on which all renal excretory processes depend, fluctuates over a wide range of amplitudes and frequencies. Much of this variation originates in nonrenal vascular beds to support nonrenal tasks, and the fluctuations provide a noisy environment in which the kidney is obliged to operate. Were it not for renal blood flow autoregulation, it would be difficult to regulate renal excretory processes so as to maintain whole body variables within narrow bounds. Autoregulation is the noise filter on which other renal processes depend for maintaining a relatively noise-free environment in which to work. Because of the time-varying nature of the blood pressure, we have concentrated in this review on the now substantial body of work on the dynamics of renal blood flow regulation and the underlying mechanisms. Renal vascular control mechanisms are not simply reactive but have their own spontaneous dynamics. Both TGF and the myogenic mechanism oscillate autonomously. The TGF oscillation is the better understood of the two. There is an oscillation of tubular pressure, proximal tubular flow, early distal Cl- concentration, and efferent arteriolar blood flow at approximately 35 mHz; all these variables are synchronized when the measurements are made in a single tubule. The autonomous nature of the oscillation is supported by simulations of the nephron and its vasculature, which show that for a reasonable representation of the dynamics of these structures and of the parameters that govern their behavior, the solutions of the equation set are periodic at the frequency of the observed oscillation, and with the same phase relationships among its variables. The simulations also show that the critical variables for the development of the oscillation are the open-loop gain of the feedback system, and the various delays in the system of which convective transport in the axis of the thick ascending limb and signal transmission between the macula densa and the afferent arteriole are the most important. The oscillation in TGF is an example of nonlinear dynamical behavior and is yet another in a long list of oscillations and related dynamics arising in the inherently nonlinear properties of living systems. Some nonlinear systems can bifurcate to states known collectively as deterministic chaos, and TGF is a clear example of such a system. Rats with two different and unrelated forms of experimental hypertension provide tubular pressure records that pass statistical tests for ordered structure and sensitive dependence on initial conditions in the reconstructed state space, two of the hallmarks of deterministic chaos. These records also pass recent more stringent tests for chaos. The significance of deterministic chaos in the context of renal blood flow regulation is that the system regulating blood flow undergoes a physical change to a different dynamical state, and because the change is deterministic, there is every expectation that the critical change will yield itself to experimental discovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

On the efficacy of linear system analysis of renal autoregulation in rats.

In order to assess the linearity of the mechanisms subserving renal blood flow autoregulation, broad-band arterial pressure fluctuations at three different power levels were induced experimentally and the resulting renal blood flow responses were recorded. Linear system analysis methods were applied in both the time and frequency domain. In the frequency domain, spectral estimates employing FFT, autoregressive moving average (ARMA) and moving average (MA) methods were used; only the MA model showed two vascular control mechanisms active at 0.02-0.05 Hz and 0.1-0.18 Hz consistent with previous experimental findings [Holstein-Rathlou et al., Amer. J. Physiol., vol. 258, 1990.]. In the time domain, impulse response functions obtained from the MA model indicated likewise the presence of these two vascular control mechanisms, but the ARMA model failed to show any vascular control mechanism at 0.02-0.05 Hz. The residuals (i.e., model prediction errors) of the MA model were smaller than the ARMA model for all levels of arterial pressure forcings. The observed low coherence values and the significant model residuals in the 0.02-0.05 Hz frequency range suggest that the tubuloglomerular feedback (TGF) active in this frequency range is a nonlinear vascular control mechanism. In addition, experimental results suggest that the operation of the TGF mechanism is more evident at low/moderate pressure fluctuations and becomes overwhelmed when the arterial pressure forcing is too high.

Animals↗

PubMed1993

Differences in dynamic autoregulation of renal blood flow between SHR and WKY rats.

In halothane-anesthetized Wistar-Kyoto (WKY) rats the single-nephron blood flow and the proximal tubule pressure oscillate at a frequency of 35-50 mHz because of the operation of the tubuloglomerular feedback (TGF) mechanism. In spontaneously hypertensive rats (SHR) the oscillations are replaced by chaotic fluctuations. We sought to determine whether this change was associated with a change in the dynamic autoregulation of renal blood flow. In halothane-anesthetized 250- to 320-g SHR and WKY rats, renal blood flow was measured during "white noise" forcing of arterial blood pressure. The frequency response of renal vascular admittance was estimated by the method of autoregressive-moving averages. In the frequency band below 60-70 mHz there was a significant difference in the transfer functions between the two strains of rats. This was due mainly to an increased phase difference, but also to a decreased magnitude of the admittance in SHR at frequencies below 20-30 mHz. Above 70 mHz there was no significant difference in the transfer functions. Because TGF is active in the low frequency band (below approximately 100 mHz), whereas the myogenic mechanism also acts in the higher frequency band, we conclude that the change in the dynamics of TGF leads to a change in the dynamic autoregulation of renal blood flow between SHR and WKY rats. This change results in a more efficient dynamic autoregulation of renal blood flow in the SHR compared with the WKY rats. The functional consequences of this, in terms of the regulation of salt and water excretion, are not presently known.

Animals↗

PubMed1993

Mechanisms of temporal variation in single-nephron blood flow in rats.

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.

Animals↗

PubMed1993

Oscillations and chaos in renal blood flow control.

In normotensive, halothane-anesthetized rats, oscillations can be found both in the single-nephron blood flow and in the tubular pressure. Experimental data and computer simulations support the hypothesis that the oscillations are caused by the tubuloglomerular feedback (TGF) mechanism. Model studies show that the key parameters determining the stability of the TGF system are the open loop gain of the system and the time delays in the signal transmission through the various components of the feedback loop. Within a broad range of parameters, the system is unstable and has self-sustained stable oscillations. The parameter range where model studies show instability overlaps with the physiologic range for the values of the same parameters. The system appears to be poised on the border between stability and oscillation, and a small parameter change may cause the system to move from one state to the other. In renovascular and spontaneously hypertensive rats, regular oscillations give way to highly irregular, chaotic fluctuations. The chaotic fluctuations appear to have the same mechanism as the regular TGF-mediated oscillations. The irregular fluctuations most likely represent a parameter-dependent transition from a limit cycle (regular oscillation) to deterministic chaos. The key parameters causing the transition have not been identified. Associated with the difference in the dynamics of TGF between normotensive and hypertensive rats is a change in the dynamic autoregulation of total RBF. This is especially prominent in the frequency range in which TGF operates, and it is suggested that a causal relationship may exist between the two phenomena. This difference may play a role in the pathogenesis of hypertension by altering the renal response to the normal fluctuations in arterial pressure.

Animals↗

PubMed1992

Dynamics of TGF-initiated nephron-nephron interactions in normotensive rats and SHR.

Proximal tubular pressure, glomerular filtration rate, and early distal tubule Cl- oscillate at 35 mHz in normotensive rats because of tubuloglomerular feedback (TGF); the oscillation bifurcates to chaos in spontaneously hypertensive rats (SHR). To examine the importance of TGF-initiated vascular interactions between nephrons in these dynamics, we measured tubular pressure simultaneously in two or more nephrons. The oscillations were synchronized in nephrons supplied by a common cortical radial artery. The correlation coefficient of pressure records from coupled nephrons was 0.86 +/- 0.02. Intratubular furosemide perfusion diminished the oscillation in both the perfused and the coupled nephron; total autospectral power in each of the nephrons and cross-spectral power were reduced to 45% of control. The correlation between noncoupled nephrons was not significant, and intratubular furosemide perfused in one nephron had no effect on adjacent but noncoupled nephrons. In SHR, the correlation coefficient of tubular pressure records was high from coupled nephrons only; furosemide diminished the autospectral power of pressure fluctuations to approximately 60-75% of control in both perfused and coupled nephrons, and cross-spectral power was affected by a similar amount. Nephron-nephron interactions, specific to vascular connectivity, persist in SHR and appear to be stronger than in normotensive rats.

Animals↗

PubMed1992

Dynamic aspects of the tubuloglomerular feedback mechanism.

Tubuloglomerular feedback (TGF) is an important intrarenal regulatory mechanism, which acts to stabilize renal blood flow, GFR, and the tubular flow rate. The anatomical basis for this negative feedback system is the Juxtaglomerular Apparatus (JGA). This is located at the point of contact between the thick ascending limb of the loop of Henle (TAL) and the vascular pole of the glomerulus. The JGA includes the macula densa, a specialized plaque of cells in the TAL thought to be responsible for the sensing step in the feedback mechanism; the mesangial cells, a cushion of cells separating the macula densa from the vascular pole of the glomerulus; and the afferent arteriole, the main effector site for the TGF. An increase in the NaCl concentration at the macula densa elicits a response in the smooth muscle cells of the afferent arteriole increasing the hemodynamic resistance of the preglomerular vasculature. These changes will, through decreases in the GFR and the tubular flow rate, cause a decrease in the NaCl concentration at the macula densa. Thus, the system acts to stabilize the NaCl concentration at the macula densa. The purpose of the present study was to describe the dynamic characteristics of the TGF, and to use this knowledge in elucidating the role of the TGF system in the autoregulation of renal blood flow. Further, by comparing the dynamic characteristics of TGF between hypertensive and normotensive rats, to identify possible alterations in renal function that could play a role in the etiology and pathogenesis of hypertension. Anesthesia and surgery are unavoidable complications in experimental work in animals. It is shown that the anesthetics commonly used in micropuncture experiments in rats have different effects on various aspects of renal function, e.g. GFR, sodium excretion, proximal tubular compliance, and TGF function. It is concluded that the thiobarbiturate inactin, the most used anesthetic, has more detrimental effects on renal function than halothane and other barbiturates. In halothane anesthetized rats, the proximal tubular pressure oscillates with a frequency of 30-50 mHz. The pressure oscillations are associated with oscillations in tubular flow, and the early distal tubular Cl- activity. The possible mechanisms behind the oscillations are discussed. It is concluded that the oscillations appear because of the operation of the TGF system. Although it seems unlikely, it cannot be excluded that a vascular pacemaker is involved in the underlying oscillatory mechanism. To test the hypothesis that the oscillations are caused by the TGF system, a series of dynamic mathematical models of the TGF system have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, General↗

PubMed1991

Lithium absorption by the rabbit gall-bladder.

Lithium (Li+) absorption across the low-resistance epithelium of the rabbit gall-bladder was studied in order to elucidate possible routes and mechanisms of Li+ transfer. Li+ at a concentration of 0.4 mM in both mucosal and serosal media did not affect isosmotic mucosa-to-serosa fluid absorption. At this low concentration net mucosa-to-serosa Li+ absorption was insignificant when the ambient Na+ concentration was 115 mM, although the gall-bladder had a significant Li+ permeability (2.7 X 10(-5) cm s-1) and a significant mucosa-to-serosa Li+ gradient developed as a result of fluid absorption. Net Li+ absorption was induced at reduced mucosal Na+ concentrations (by lowering the Na+ concentration down to 50 mM with or without substitution with sucrose, or by adding sucrose to the mucosal medium). This Li+ absorption occurred even in the absence of a mucosa-to-serosa Li+ gradient. Na+ and Li+ absorptions occurring at 50 mM Na+ were inhibited to the same degree by mucosal 1 mM amiloride. Substitution of 5-50 mM (44%) Na+ by Li+ in the external medium dose-dependently depressed Na+ absorption by up to 76%, while substitution by 50 mM choline had no significant effect. Li+ inhibition of Na+ absorption was elicited from the mucosal side and was not accounted for by compensatory Li+ absorption; water and Na+ absorption rates decreased nearly in parallel. The effects of 0.4 mM amiloride and of substitution with 20 mM Li+ were only partly additive. It is concluded that Li+ absorption in the rabbit gall-bladder cannot be explained by passive (paracellular) transport, but must be the result of transcellular, active transport. Both at low and at high concentrations Li+ may enter the cell via an Na+/H+ exchanger in the apical cell membrane. At high concentrations Li+ may inhibit Na+ absorption by interference with the exchange mechanism and/or via effects at the cytoplasmic level. The Li+ transfer mechanism across the basolateral cell membrane remains unknown.

Amiloride↗

PubMed1991

Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats.

To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured. Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model correctly predicted gain and phase only in the low-frequency range. Experimental results revealed a second component of vascular control active at 100-150 mHz that was not predicted by the simulation. Forcings at single frequencies showed that the system behaves linearly except in the band of 33-50 mHz in which, in addition, there are autonomous oscillations in TGF. Higher amplitude forcings in this band were attenuated by autoregulatory mechanisms, but low-amplitude forcings entrained the autonomous oscillations and provoked amplified oscillations in blood flow, showing an effect of TGF on whole kidney blood flow. We conclude that two components can be detected in the dynamic regulation of renal blood flow, i.e., a slow component that represents TGF and a faster component that most likely represents an intrinsic vascular myogenic mechanism.

Animals↗

PubMed1991

Chaos in blood flow control in genetic and renovascular hypertensive rats.

Hydrostatic pressure and flow in renal proximal tubules oscillate at 30-40 mHz in normotensive rats anesthetized with halothane. The oscillations originate in tubuloglomerular feedback, a mechanism that provides local blood flow regulation. Instead of oscillations, spontaneously hypertensive rats (SHR) have aperiodic tubular pressure fluctuations; the pattern is suggestive of deterministic chaos. Normal rats made hypertensive by clipping one renal artery had similar aperiodic tubular pressure fluctuations in the unclipped kidney, and the fraction of rats with irregular fluctuations increased with time after the application of the renal artery clip. Statistical measures of deterministic chaos were applied to tubular pressure data. The correlation dimension, a measure of the dimension of the phase space attractor generating the time series, indicated the presence of a low-dimension strange attractor, and the largest Lyapunov exponent, a measure of the rate of divergence in phase space, was positive, indicating sensitivity to initial conditions. These time series therefore satisfy two criteria of deterministic chaos. The measures were the same in SHR as in rats with renovascular hypertension. Since two different models of hypertension displayed similar dynamics, we suggest that chaotic behavior is a common feature of renal vascular control in the natural history of the disease.

Animals↗

PubMed1991

A closed-loop analysis of the tubuloglomerular feedback mechanism.

The tubuloglomerular feedback (TGF) mechanism is of importance in the regulation of glomerular filtration rate (GFR). A second mechanism of potential importance is the change in proximal pressure caused by a change, for example, in the rate of proximal fluid reabsorption. The quantitative contributions of these two mechanisms to the regulation of GFR and the late proximal flow rate are not known. To determine the regulatory efficiency of these two mechanisms, the late proximal flow rate was perturbed by microperfusion with artificial tubular fluid in halothane-anesthetized Sprague-Dawley rats. The resulting changes in late proximal flow rate were measured by pulse injection of rhodamine dextran. Fluorescence was excited by means of a He-Ne laser. Bolus velocity was measured by videomicroscopy. Tubular pressure was measured by the servonulling method. The microperfusion rate was varied from -15 to 20 nl/min in steps of 5 nl/min. The open-loop gain (OLG) was 3.1 (range 1.5-9.9, n = 13) at the unperturbed tubular flow rate, and decreased as the tubular flow rate was either increased or decreased. The proximal pressure increased by 0.21 +/- 0.03 mmHg per unit increase in late proximal flow rate (nl/min). By use of a mathematical model of the glomerulus, it is estimated that under the present experimental conditions the pressure increase contributes 8% (range 3-15%) of the OLG. It is concluded that, for small perturbations around the operating point, TGF accounts for most of the regulation of GFR and the late proximal flow rate, with changes in the proximal pressure of lesser importance. Furthermore, under closed-loop conditions the operating point for the TGF mechanism is at or close to the point of maximal sensitivity.

Animals↗