scholarly journals Dynamic characteristics and underlying mechanisms of renal blood flow autoregulation in the conscious dog

2001 ◽  
Vol 280 (6) ◽  
pp. F1062-F1071 ◽  
Author(s):  
Armin Just ◽  
Heimo Ehmke ◽  
Lira Toktomambetova ◽  
Hartmut R. Kirchheim
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Time Course ◽  
External Iliac Artery ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Myogenic Response ◽  
Pressure Step

The time course of the autoregulatory response of renal blood flow (RBF) to a step increase in renal arterial pressure (RAP) was studied in conscious dogs. After RAP was reduced to 50 mmHg for 60 s, renal vascular resistance (RVR) decreased by 50%. When RAP was suddenly increased again, RVR returned to baseline with a characteristic time course (control; n = 15): within the first 10 s, it rose rapidly to 70% of baseline ( response 1), thus already comprising 40% of the total RVR response. Thereafter, it increased at a much slower rate until it started to rise rapidly again at 20–30 s after the pressure step ( response 2). After passing an overshoot of 117% at 43 s, RVR returned to baseline values. Similar responses were observed after RAP reduction for 5 min or after complete occlusions for 60 s. When tubuloglomerular feedback (TGF) was inhibited by furosemide (40 mg iv, n = 12), response 1 was enhanced, providing 60% of the total response, whereas response 2 was completely abolished. Instead, RVR slowly rose to reach the baseline at 60 s ( response 3). The same pattern was observed when furosemide was given at a much higher dose (>600 mg iv; n = 6) or in combination with clamping of the plasma levels of nitric oxide ( n = 6). In contrast to RVR, vascular resistance in the external iliac artery after a 60-s complete occlusion started to rise with a delay of 4 s and returned to baseline within 30 s. It is concluded that, in addition to the myogenic response and the TGF, a third regulatory mechanism significantly contributes to RBF autoregulation, independently of nitric oxide. The three mechanisms contribute about equally to resting RVR. The myogenic response is faster in the kidney than in the hindlimb.

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.

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.

A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice

2007 ◽  
Vol 293 (5) ◽  
pp. F1489-F1500 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Adenosine Receptors ◽  
Time Course ◽  
Tubuloglomerular Feedback ◽  
The Third ◽  
A1 Adenosine Receptors ◽  
The Impact ◽  
Renal Blood Flow Autoregulation

Autoregulation of renal blood flow (RBF) is mediated by a fast myogenic response (MR; ∼5 s), a slower tubuloglomerular feedback (TGF; ∼25 s), and potentially additional mechanisms. A1 adenosine receptors (A1AR) mediate TGF in superficial nephrons and contribute to overall autoregulation, but the impact on the other autoregulatory mechanisms is unknown. We studied dynamic autoregulatory responses of RBF to rapid step increases of renal artery pressure in mice. MR was estimated from autoregulation within the first 5 s, TGF from that at 5–25 s, and a third mechanism from 25–100 s. Genetic deficiency of A1AR (A1AR−/−) reduced autoregulation at 5–25 s by 50%, indicating a residual fourth mechanism resembling TGF kinetics but independent of A1AR. MR and third mechanism were unaltered in A1AR−/−. Autoregulation in A1AR−/− was faster at 5–25 than at 25–100 s suggesting two separate mechanisms. Furosemide in wild-type mice (WT) eliminated the third mechanism and enhanced MR, indicating TGF-MR interaction. In A1AR−/−, furosemide did not further impair autoregulation at 5–25 s, but eliminated the third mechanism and enhanced MR. The resulting time course was the same as during furosemide in WT, indicating that A1AR do not affect autoregulation during furosemide inhibition of TGF. We conclude that at least one novel mechanism complements MR and TGF in RBF autoregulation, that is slower than MR and TGF and sensitive to furosemide, but not mediated by A1AR. A fourth mechanism with kinetics similar to TGF but independent of A1AR and furosemide might also contribute. A1AR mediate classical TGF but not TGF-MR interaction.

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.

scholarly journals Continuously measured renal blood flow does not increase in diabetes if nitric oxide synthesis is blocked

2008 ◽  
Vol 295 (5) ◽  
pp. F1449-F1456 ◽  
Author(s):  
Tracy D. Bell ◽  
Gerald F. DiBona ◽  
Rachel Biemiller ◽  
Michael W. Brands
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Function Analysis ◽  
Control Period ◽  
Power Spectra ◽  
Tubuloglomerular Feedback ◽  
Left Renal Artery ◽  
Renal Vasculature ◽  
Transfer Function Analysis

This study used 16 h/day measurement of renal blood flow (RBF) and arterial pressure (AP) to determine the role of nitric oxide (NO) in mediating the renal vasodilation caused by onset of type 1 diabetes. The AP and RBF power spectra were used to determine the autoregulatory efficiency of the renal vasculature. Rats were instrumented with artery and vein catheters and a Transonic flow probe on the left renal artery and were divided randomly into four groups: control (C), diabetes (D), control plus nitro-l-arginine methyl ester (l-NAME; CL), and diabetes plus l-NAME (DL). Mean AP averaged 90 ± 1 and 121 ± 1 mmHg in the D and DL groups, respectively, during the control period, and RBF averaged 5.9 ± 1.2 and 5.7 ± 0.7 ml/min, respectively. Respective C and CL groups were not different. Onset of diabetes (streptozotocin 40 mg/kg iv) in D rats increased RBF gradually, but it averaged 55% above control by day 14. In DL rats, on the other hand, RBF remained essentially constant, tracking with RBF in the nondiabetic C and CL groups for the 2-wk period. Diabetes did not change mean AP in any group. Transfer function analysis revealed impaired dynamic autoregulation of RBF overall, including the frequency range of tubuloglomerular feedback (TGF), and l-NAME completely prevented those changes as well. These data strongly support a role for NO in causing renal vasodilation in diabetes and suggest that an effect of NO to blunt RBF autoregulation may play an important role.

Canine renal vascular response to hyperoncotic dextran in kidneys with or without glomerular filtration

1983 ◽  
Vol 245 (6) ◽  
pp. F687-F690
Author(s):  
R. W. Gotshall
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Vascular Response ◽  
Anesthetized Dogs ◽  
Tubular Flow ◽  
Renal Vascular

The effect of intrarenal arterial infusion of hyperoncotic dextran on renal hemodynamics and excretion was studied in anesthetized dogs. To examine the role of glomerular filtration and tubular flow in the hemodynamic response, several kidney models were employed. Nonfiltering kidneys (NFK) were produced by combined ischemia and ureteral obstruction (UO). Additionally, kidneys with only UO and a lack of filtration as well as kidneys with only ischemia and glomerular filtration were studied. Renal blood flow in normal kidneys was increased by hyperoncotic dextran from 357 +/- 47 to 486 +/- 65 ml X min-1 X 100 g-1, with a corresponding decrease in renal vascular resistance. Ischemic kidneys responded likewise to the dextran infusion, increasing renal blood flow from 261 +/- 31 to 339 +/- 29 ml X min-1 X 100 g-1. Glomerular filtration rate was reduced by the dextran infusion from 80.1 +/- 7.9 to 60.7 +/- 6.6 in normal kidneys and from 31.8 +/- 9.6 to 20.2 +/- 5.8 ml X min-1 X 100 g-1 in ischemic kidneys. Urine flow and sodium excretion were also reduced in these kidneys. In contrast, both NFK and UO, which lacked filtration and tubular flow, did not vasodilate in response to dextran. Renal blood flow remained unchanged from control values (NFK: 146 +/- 6, UO: 111 +/- 22 ml X min-1 X 100 g-1) in these kidneys. These experiments show that the renal vascular response to hyperoncotic dextran is not due to a change in blood volume or viscosity nor to a direct pharmacologic action of dextran. The most likely explanation is that hyperoncotic dextran alters tubuloglomerular feedback control of renal vascular resistance by decreasing filtration and altering tubular flow and/or composition. However, the involvement of another intrarenal vasodilatory system cannot be discounted.

Dynamics and contribution of mechanisms mediating renal blood flow autoregulation

2003 ◽  
Vol 285 (3) ◽  
pp. R619-R631 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Response Times ◽  
Slow Component ◽  
Regulatory System ◽  
Tubuloglomerular Feedback ◽  
Maximum Speed ◽  
Myogenic Response ◽  
Total Response ◽  
Relative Contribution

We investigated dynamic characteristics of renal blood flow (RBF) autoregulation and relative contribution of underlying mechanisms within the autoregulatory pressure range in rats. Renal arterial pressure (RAP) was reduced by suprarenal aortic constriction for 60 s and then rapidly released. Changes in renal vascular resistance (RVR) were assessed following rapid step reduction and RAP rise. In response to rise, RVR initially fell 5-10% and subsequently increased ∼20%, reflecting 93% autoregulatory efficiency (AE). Within the initial 7-9 s, RVR rose to 55% of total response providing 37% AE, reaching maximum speed at 2.2 s. A secondary RVR increase began at 7-9 s and reached maximum speed at 10-15 s. Response times suggest that the initial RVR reflects the myogenic response and the secondary tubuloglomerular feedback (TGF). During TGF inhibition by furosemide, AE was 64%. The initial RVR rise was accelerated and enhanced, providing 49% AE, but it represented only 88% of total. The remaining 12% indicates a third regulatory component. The latter contributed up to 50% when the RAP increase began below the autoregulatory range. TGF augmentation by acetazolamide affected neither AE nor relative myogenic contribution. Diltiazem infusion markedly inhibited AE and the primary and secondary RVR increases but left a slow component. In response to RAP reduction, initial vasodilation constituted 73% of total response but was not affected by furosemide. The third component's contribution was 9%. Therefore, RBF autoregulation is primarily due to myogenic response and TGF, contributing 55% and 33-45% in response to RAP rise and 73% and 18-27% to RAP reduction. The data imply interaction between TGF and myogenic response affecting strength and speed of myogenic response during RAP rises. The data suggest a third regulatory system contributing <12% normally but up to 50% at low RAP; its nature awaits further investigation.

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

1995 ◽  
Vol 269 (4) ◽  
pp. F581-F593 ◽  
Author(s):  
R. Feldberg ◽  
M. Colding-Jorgensen ◽  
N. H. Holstein-Rathlou
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Renal Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Distributed Model ◽  
Myogenic Response ◽  
Control Mechanisms ◽  
Afferent Arteriole ◽  
Vascular Effects ◽  
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.

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