scholarly journals Altered whole kidney blood flow autoregulation in a mouse model of reduced β-ENaC

2010 ◽  
Vol 298 (2) ◽  
pp. F285-F292 ◽  
Author(s):  
Samira C. Grifoni ◽  
Rumbidzayi Chiposi ◽  
Susan E. McKey ◽  
Michael J. Ryan ◽  
Heather A. Drummond
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Mouse Model ◽  
Tubuloglomerular Feedback ◽  
Initial Increase ◽  
Myogenic Response ◽  
Kidney Blood Flow ◽  
Induced Changes ◽  
Renal Vascular

Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (∼5 s) and slow acting tubuloglomerular feedback (TGF; ∼25 s). Previous studies suggest epithelial Na+ channel (ENaC) family proteins, β-ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown whether β-ENaC-mediated myogenic constriction contributes to RBF autoregulation in vivo. Therefore, the goal of this investigation was to determine whether the myogenic mediated RBF autoregulation is inhibited in a mouse model of reduced β-ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-min step increase in mean arterial pressure (MAP). Pressure-induced changes in RBF and RVR at 0–5, 6–25, and 110–120 s after step increase in MAP were used to assess the contribution of myogenic and TGF mechanisms and steady-state autoregulation, respectively. The rate of the initial increase in RVR, attributed to the myogenic mechanism, was reduced by ∼50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady-state autoregulation was similar between β-ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in β-ENaC +/+ and m/m mice, however, it occurred over a longer period (+10 s), which may have allowed TGF to compensate for a loss in myogenic autoregulation. Our findings suggest β-ENaC is an important mediator of renal myogenic constriction-mediated RBF autoregulation in vivo.

scholarly journals Aging Impairs Renal Autoregulation in Mice

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Jin Wei ◽  
Jinxiu Zhu ◽  
Jie Zhang ◽  
Shan Jiang ◽  
Larry Qu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Myogenic Response ◽  
Renal Autoregulation ◽  
Integrin Α5 ◽  
Aging Kidney

Impaired renal autoregulation permits more transmission of disturbance in systemic blood pressure, which initiates barotrauma in intrarenal microvasculatures such as glomerular and tubulointerstitial capillaries, contributing to the development of kidney damage and deterioration in renal function, especially under the conditions with high blood pressure. Although it has been postulated that autoregulatory efficiency is attenuated in the aging kidney, direct evidence remains lacking. In the present study, we measured the autoregulation of renal blood flow, myogenic response of afferent arteriole (Af-Art), tubuloglomerular feedback in vivo with micropuncture, as well as tubuloglomerular feedback in vitro in isolated perfused juxtaglomerular apparatus in young and aged C57BL/6 mice. We found that renal blood flow was not significantly changed in response to a defined elevation of renal arterial pressure in young mice but significantly increased in aged mice. Additionally, myogenic response of Af-Art measured by microperfusion with a stepwise increase in perfusion pressure was significantly blunted in the aging kidney, which is associated with the attenuation of intraluminal pressure-induced intracellular calcium increases, as well as the reduced expression of integrin α5 (Itga5) in Af-Art. Moreover, both tubuloglomerular feedback in vivo and in vitro were nearly inactive in the aging kidney, which is associated with the significantly reduced expression of adenosine A1 receptor (A1AR) and suppressed vasoconstrictor response to adenosine in Af-Art. In conclusion, this study demonstrates that aging impairs renal autoregulation with blunted myogenic response and inhibited tubuloglomerular feedback response. The underlying mechanisms involve the downregulations of integrin α5 and A1AR in the Af-Art.

Tubuloglomerular feedback and blood flow autoregulation during DA1-induced renal vasodilation

1990 ◽  
Vol 258 (3) ◽  
pp. F627-F635 ◽  
Author(s):  
D. M. Pollock ◽  
W. J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Feedback Control ◽  
Arterial Pressure ◽  
Receptor Activation ◽  
Tubuloglomerular Feedback ◽  
Doppler Flowmetry ◽  
Single Nephron ◽  
Electromagnetic Flow Probe ◽  
Induced Changes ◽  
Renal Vascular

The effect of renal vasodilation produced by the dopamine DA1-receptor agonist, fenoldopam (SKF-82526), on tubuloglomerular feedback (TGF) activity and the autoregulation of renal blood flow (RBF) was determined in euvolemic rats. Fenoldopam (2.5 micrograms.kg-1.min-1 iv) increased RBF by 17% (electromagnetic flow probe) while glomerular filtration rate (GFR) was unchanged; mean arterial pressure was decreased by 6%. Superficial cortical blood flow was increased by 12% (laser-Doppler flowmetry) while single-nephron GFR (SNGFR) and estimated glomerular capillary pressure (stop-flow pressure, Psf) were stable. SNGFR measured at proximal and distal sites along the same nephron was not affected by fenoldopam. Partial inhibition of TGF was indicated by the constancy of distal SNGFR and the proximal-distal SNGFR difference in the presence of increased distal delivery of native fluid. However, fenoldopam did not affect feedback control of Psf evaluated by perfusing artificial fluid through Henle's loop at 0-62 nl/min. Despite the decrease in renal vascular resistance over an arterial pressure range of 130 to 70 mmHg, RBF was autoregulated efficiently during fenoldopam infusion. These results indicate that DA1-receptor activation dilates the preglomerular and efferent arterioles without affecting GFR or glomerular pressure. However, this vasodilatory mechanism operates independent of autoregulation and TGF-induced changes in glomerular pressure such that preglomerular vessels remain responsive to the appropriate signals from these intrinsic control systems. The ability of fenoldopam to blunt feedback control of SNGFR may depend on changes in the filtration coefficient independent of glomerular pressure and/or a constituent of natural tubular fluid.

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

2007 ◽  
Vol 293 (1) ◽  
pp. F279-F287 ◽  
Author(s):  
Mona Oppermann ◽  
Pernille B. Hansen ◽  
Hayo Castrop ◽  
Jurgen Schnermann
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Tubuloglomerular Feedback ◽  
Intact Mouse ◽  
Peritubular Capillaries ◽  
Intact Kidney ◽  
Afferent Arterioles ◽  
Renal Vascular ◽  
Dose Dependent Increase

Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or NG-nitro-l-arginine methyl ester, furosemide caused a dose-dependent increase of vascular diameter, but it was without effect in vessels from NKCC1−/− mice suggesting that inhibition of NKCC1 mediates dilatation in afferent arterioles. In the intact kidney, however, furosemide (2 mg/kg iv) caused a 50.5 ± 3% reduction of total renal blood flow (RBF) and a 27% reduction of superficial blood flow (SBF) accompanied by a marked and immediate increase of tubular pressure and volume. At 10 mg/kg, furosemide reduced RBF by 60.4 ± 2%. Similarly, NKCC1−/− mice responded to furosemide with a 45.4% decrease of RBF and a 29% decrease of SBF. Decreases in RBF and SBF and increases of tubular pressure by furosemide were ameliorated by renal decapsulation. In addition, pretreatment with candesartan (2 mg/kg) or indomethacin (5 mg/kg) attenuated the reduction of RBF and peak urine flows caused by furosemide. Our data indicate that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular capillaries by the expanding tubular compartment are responsible for the reduction of RBF in vivo.

scholarly journals Monitoring of rhythms in laser speckle data

2014 ◽  
Vol 07 (03) ◽  
pp. 1450015 ◽  
Author(s):  
D. E. Postnov ◽  
A. Y. Neganova ◽  
D. D. Postnov ◽  
A. R. Brazhe
Keyword(s):  
Blood Flow ◽  
Graphics Processing Units ◽  
Surrogate Data ◽  
Laser Speckle ◽  
Tubuloglomerular Feedback ◽  
Additional Information ◽  
3D Data ◽  
Kidney Blood Flow ◽  
Rhythm Analysis ◽  
Spatio Temporal

While the laser speckle imaging (LSI) is a powerful tool for multiple biomedical applications, such as monitoring of the blood flow, in many cases it can provide additional information when combined with spatio-temporal rhythm analysis. We demonstrate the application of Graphics Processing Units (GPU)-based rhythm analysis for the post processing of LSI data, discuss the relevant structure of GPU-based computations, test the proposed technique on surrogate 3D data, and apply this approach to kidney blood flow autoregulation. Experiments with surrogate data demonstrate the ability of the method to extract information about oscillation patterns from noisy data, as well as to detect the moving source of the rhythm. The analysis of kidney data allow us to detect and to localize the dynamics arising from autoregulation processes at the level of individual nephrons (tubuloglomerular feedback (TGF) rhythm), as well as to distinguish between the TGF-active and the TGF-silent zones.

A novel mouse model based on intersectional genetics enables unambiguous in vivo discrimination between plasmacytoid and other dendritic cells and their comparative characterization

2022 ◽  
Author(s):  
Michael Valente ◽  
Nils Collinet ◽  
Thien-Phong Vu Manh ◽  
Karima Naciri ◽  
Gilles Bessou ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Mouse Model ◽  
Single Cell ◽  
Ex Vivo ◽  
High Specificity ◽  
Type I ◽  
Specific Expression ◽  
Physiological Functions

Plasmacytoid dendritic cells (pDC) were identified about 20 years ago, based on their unique ability to rapidly produce copious amounts of all subsets of type I and type III interferon (IFN-I/III) upon virus sensing, while being refractory to infection. Yet, the identity and physiological functions of pDC are still a matter of debate, in a large part due to their lack of specific expression of any single cell surface marker or gene that would allow to track them in tissues and to target them in vivo with high specificity and penetrance. Indeed, recent studies showed that previous methods that were used to identify or deplete pDC also targeted other cell types, including pDC-like cells and transitional DC (tDC) that were proposed to be responsible for all the antigen presentation ability previously attributed to steady state pDC. Hence, improving our understanding of the nature and in vivo choreography of pDC physiological functions requires the development of novel tools to unambiguously identify and track these cells, including in comparison to pDC-like cells and tDC. Here, we report successful generation of a pDC-reporter mouse model, by using an intersectional genetic strategy based on the unique co-expression of Siglech and Pacsin1 in pDC. This pDC-Tomato mouse strain allows specific ex vivo and in situ detection of pDC. Breeding them with Zbtb46GFP mice allowed side-by-side purification and transcriptional profiling by single cell RNA sequencing of bona fide pDC, pDC-like cells and tDC, in comparison to type 1 and 2 conventional DC (cDC1 and cDC2), both at steady state and during a viral infection, revealing diverging activation patterns of pDC-like cells and tDC. Finally, by breeding pDC-Tomato mice with Ifnb1EYFP mice, we determined the choreography of pDC recruitment to the micro-anatomical sites of viral replication in the spleen, with initially similar but later divergent behaviors of the pDC that engaged or not into IFN-I production. Our novel pDC-Tomato mouse model, and newly identified gene modules specific to combinations of DC types and activations states, will constitute valuable resources for a deeper understanding of the functional division of labor between DC types and its molecular regulation at homeostasis and during viral infections.

Abstract 062: Regulation of Nephron Afferent Arteriole Resistance in Obesity: Role of Connecting Tubule Glomerular Feedback

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sumit R Monu ◽  
Mani Maheshwari ◽  
Hong Wang ◽  
Ed Peterson ◽  
Oscar Carretero
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Afferent Arteriole ◽  
Connecting Tubule ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
The Difference

In obesity, renal damage is caused by increase in renal blood flow (RBF), glomerular capillary pressure (P GC ), and single nephron glomerular filtration rate but the mechanism behind this alteration in renal hemodynamics is unclear. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance is regulated by mechanism similar to that in other arterioles and in addition, it is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via sodium–potassium-2-chloride cotransporter-2 (NKCC2) and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation and is mediated by connecting tubule via epithelial sodium channel (ENaC). CTGF is blocked by the ENaC inhibitor benzamil. Attenuation of TGF reduces Af-Art resistance and allows systemic pressure to get transmitted to the glomerulus that causes glomerular barotrauma/damage. In the current study, we tested the hypothesis that TGF is attenuated in obesity and that CTGF contributes to this effect. We used Zucker obese rats (ZOR) while Zucker lean rats (ZLR) served as controls. We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min in stepwise manner.CTGF was calculated as the difference of P SF value between vehicle and benzamil treatment, at each perfusion rate. Maximal TGF response was significantly less in ZOR (6.16 ± 0.52 mmHg) when compared to the ZLR (8.35 ± 1.00mmHg), p<0.05 , indicating TGF resetting in the ZOR. CTGF was significantly higher in ZOR (6.33±1.95 mmHg) when compared to ZLR (1.38±0.89 mmHg), p<0.05 . When CTGF was inhibited with the ENaC blocker Benzamil (1μM), maximum P SF decrease was 12.30±1.72 mmHg in ZOR and 10.60 ± 1.73 mmHg in ZLR, indicating that blockade of CTGF restored TGF response in ZOR. These observations led us to conclude that TGF is reset in ZOR and that enhanced CTGF contributes to this effect. Increase in CTGF may explain higher renal blood flow, increased P GC and higher glomerular damage in obesity.

Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs

1999 ◽  
Vol 276 (3) ◽  
pp. F442-F449 ◽  
Author(s):  
Armin Just ◽  
Heimo Ehmke ◽  
Uwe Wittmann ◽  
Hartmut R. Kirchheim
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Transfer Functions ◽  
High Gain ◽  
Tubuloglomerular Feedback ◽  
Myogenic Response ◽  
No Donor ◽  
The Mean ◽  
Spontaneous Fluctuations ◽  
Elevated Heart Rate

The aim of this study was to investigate the influence of the mean level and phasic modulation of NO on the dynamic autoregulation of renal blood flow (RBF). Transfer functions were calculated from spontaneous fluctuations of RBF and arterial pressure (AP) in conscious resting dogs for 2 h under control conditions, after NO synthase (NOS) inhibition [ N G-nitro-l-arginine methyl ester hydrochloride (l-NAME)] and afterl-NAME followed by a continuous infusion of an NO donor [ S-nitroso- N-acetyl-dl-penicillamine (SNAP)]. After l-NAME ( n = 7) AP was elevated, heart rate (HR) and RBF were reduced. The gain of the transfer function above 0.08 Hz was increased, compatible with enhanced resonance of the myogenic response. A peak of high gain around 0.03 Hz, reflecting oscillations of the tubuloglomerular feedback (TGF), was not affected. The gain below 0.01 Hz, was elevated, but still less than 0 dB, indicating diminished but not abolished autoregulation. Afterl-NAME and SNAP ( n = 5), mean AP and RBF were not changed, but HR was slightly elevated. The gain above 0.08 Hz and the peak of high gain at 0.03 Hz were not affected. The gain below 0.01 Hz was elevated, but smaller than 0 dB. It is concluded that NO may help to prevent resonance of the myogenic response depending on the mean level of NO. The feedback oscillations of the TGF are not affected by NO. NO contributes to the autoregulation below 0.01 Hz due to phasic modulation independent of its mean level.

The step response: a method to characterize mechanisms of renal blood flow autoregulation

2003 ◽  
Vol 285 (4) ◽  
pp. F758-F764 ◽  
Author(s):  
T. Wronski ◽  
E. Seeliger ◽  
P. B. Persson ◽  
C. Forner ◽  
C. Fichtner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renal Perfusion ◽  
Oscillation Period ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Myogenic Response ◽  
Renal Vasculature ◽  
The Individual ◽  
Reported Data

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow (RBF) is mediated by the rapid myogenic response, by the slower tubuloglomerular feedback (TGF) mechanism, and, possibly, by an even slower third mechanism. To evaluate the individual contribution of these mechanisms to RBF autoregulation, we analyzed the response of RBF to a step increase in RPP. In anesthetized rats, the suprarenal aorta was occluded for 30 s, and then the occlusion was released to induce a step increase in RPP. Three dampened oscillations were observed; their oscillation periods ranged from 9.5 to 13 s, from 34.2 to 38.6 s, and from 100.5 to 132.2 s, respectively. The two faster oscillations correspond with previously reported data on the myogenic mechanism and the TGF. In accordance, after furosemide, the amplitude of the intermediate oscillation was significantly reduced. Inhibition of nitric oxide synthesis by Nω-nitro-l-arginine methyl ester significantly increased the amplitude of the 10-s oscillation. It is concluded that the parameters of the dampened oscillations induced by the step increase in RPP reflect properties of autoregulatory mechanisms. The oscillation period characterizes the individual mechanism, the dampening is a measure for the stability of the regulation, and the square of the amplitudes characterizes the power of the respective mechanism. In addition to the myogenic response and the TGF, a third rather slow mechanism of RBF autoregulation exists.

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