TGF‐mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar‐Kyoto rats

Holstein‐Rathlou, Niels‐Henrik; Leyssac, P. P.

doi:10.1111/j.1748-1716.1986.tb07824.x

Cited by 123 publications

(123 citation statements)

References 17 publications

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“…The net response of all factors on tubular pressure after furosemide is unpredictable. Holstein-Rathlou and Leyssac (63) reported an acute increase in tubular pressure upon intraluminal administration of furosemide of ϳ5-7 mmHg, which is relevant with respect to an estimated net ultrafiltration pressure of 20 -25 mmHg. The increase is likely due to an increase in tubular flow due to the combined effects of inhibition of loop of Henle reabsorption, and an increase in SNGFR due to inhibition of TGF.…”

Section: Questions Regarding Hemodynamics and Vascular Regulation Andmentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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Section: Questions Regarding Hemodynamics and Vascular Regulation Andmentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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“…However, in the mid-1980s, experiments by Leyssac and Baumbach 11 and by Holstein-Rathlou and Leyssac 12 demonstrated that the TGF regulation in rat nephrons tends to be unstable and to generate self-sustained oscillations in the tubular pressures and flows with a typical period of 30-40 s. While for normal rats the oscillations had the appearance of a regular self-sustained oscillation with a sharply peaked power spectrum, highly irregular oscillations, displaying a broadband spectral distribution with strong subharmonic components, were observed for spontaneously hypertensive rats. It has subsequently been found that irregular oscillations can be elicited for rats with normal blood pressure, provided that the arterial blood pressure is increased by reducing the blood flow to the other kidney ͑two-kidney, one-clip Goldblatt hypertensive rats͒.…”

Section: Pressure and Flow Control In The Kidneymentioning

confidence: 99%

Synchronization phenomena in nephron–nephron interaction

Holstein‐Rathlou

Yip

Sosnovtseva

et al. 2001

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Experimental data for tubular pressure oscillations in rat kidneys are analyzed in order to examine the different types of synchronization that can arise between neighboring functional units. For rats with normal blood pressure, the individual unit ͑the nephron͒ typically exhibits regular oscillations in its tubular pressure and flow variations. For such rats, both in-phase and antiphase synchronization can be demonstrated in the experimental data. For spontaneously hypertensive rats, where the pressure variations in the individual nephrons are highly irregular, signs of chaotic phase and frequency synchronization can be observed. Accounting for a hemodynamic as well as for a vascular coupling between nephrons that share a common interlobular artery, we develop a mathematical model of the pressure and flow regulation in a pair of adjacent nephrons. We show that this model, for appropriate values of the parameters, can reproduce the different types of experimentally observed synchronization. © 2001 American Institute of Physics. ͓DOI: 10.1063/1.1376398͔The kidneys play an essential role in regulating the blood pressure and maintaining a proper environment for the cells of the body. This control depends to a large extent on mechanisms associated with the individual functional unit, the nephron. However, a variety of cooperative phenomena that arise from interactions among the nephrons may also be important. In-phase synchronization, for instance, where the nephrons simultaneously perform the same regulatory adjustments of the incoming blood flow is likely to produce fast and strong effects in the overall response to changes in the external conditions. Out-ofphase synchronization, on the other hand, will lead to a slower and less pronounced response of the system in the aggregate. The purpose of the present paper is to demonstrate how different forms of synchronization can be observed in the pressure and flow variations for neighboring nephrons. Particularly interesting is the observation of chaotic phase synchronization in rats with high blood pressure. Based on a description of the physiological mechanisms involved in the various regulations, we develop a mathematical model that can account for the experimentally observed synchronization phenomena.

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“…However, as demonstrated in experiments on rats [40,41], this mechanism tends to be unstable and to produce large amplitude self-sustained oscillations in the tubular pressures and Àows with periods in the 30-40 sec range. The instability in the feedback and the relatively long periodicity of the oscillations are directly related to the time of 12-15 sec that it takes for the tubular Àuid to pass the loop of Henle.…”

Section: Period Doubling In Nephron Autoregulationmentioning

confidence: 99%

The transition to chaotic phase synchronization

Mosekilde

Laugesen

Zhusubaliyev

2012

AIP Conference Proceedings

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Abstract. The transition to chaotic phase synchronization for a periodically driven spiral-type chaotic oscillator is known to involve a dense set of saddle-node bifurcations. By following the synchronization transition through the cascade of period-doubling bifurcations in a forced Rössler system, this paper describes how these saddle-node bifurcations arise and how their characteristic cyclic organisation develops. We identify the cycles that are involved in the various saddle-node bifurcations and descibe how the formation of multi-layered resonance cycles in the synchronization domain is related to the torus doubling bifurcations that take place outside this domain. By examining a physiology-based model of the blood Àow regulation to the individual functional unit (nephron) of the kidney we demonstrate how a similar bifurcation structure may arise in this system as a response to a periodically varying arterial blood pressure. The paper ¿nally discusses how an alternative transition to chaotic phase synchronization may occur in the mutual synchronization of two chaotically oscillating period-doubling systems.

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TGF‐mediated oscillations in the proximal intratubular pressure: differences between spontaneously hypertensive rats and Wistar‐Kyoto rats

Cited by 123 publications

References 17 publications

Everything we always wanted to know about furosemide but were afraid to ask

Everything we always wanted to know about furosemide but were afraid to ask

Synchronization phenomena in nephron–nephron interaction

The transition to chaotic phase synchronization

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