Control of renal hemodynamics in hyperglycemia: possible role of tubuloglomerular feedback

1987 ◽  
Vol 252 (1) ◽  
pp. F65-F73 ◽  
Author(s):  
L. L. Woods ◽  
H. L. Mizelle ◽  
J. E. Hall
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Control Period ◽  
Renal Perfusion ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Renal Autoregulation ◽  
Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Renal Vascular

The purpose of this study was to test the hypothesis that hyperglycemia, comparable with that found in uncontrolled diabetes mellitus, increases renal blood flow (RBF) and glomerular filtration rate (GFR) through a tubuloglomerular feedback (TGF) mechanism. We infused glucose intrarenally (0.1-0.3 g/min) into anesthetized dogs with normal kidneys (NK), with nonfiltering kidneys (NFK) in which changes in TGF were blocked, and with normal kidneys in which renal perfusion pressure (RAP) was lowered to the limits of renal autoregulation (LPK). Calculated intrarenal plasma glucose levels rose to 250-400 mg/dl. In NK (n = 6) RBF and GFR increased by 18 +/- 3 and 19 +/- 5%, respectively, and renal vascular resistance fell by 17 +/- 2% after 90 min. The renal hemodynamic responses to glucose were abolished in NFK (n = 8); RBF averaged 96 +/- 4% of control after 60 min of hyperglycemia. RBF and GFR did not change during hyperglycemia in LPK (n = 5), averaging 96 +/- 1 and 100 +/- 8% of control, respectively, after 60 min. Autoregulation of RBF and GFR during reductions in RAP was impaired during hyperglycemia in NK; RBF and GFR were effectively autoregulated between RAP of 126 and 70-85 mmHg during the control period, whereas during glucose infusion RBF and GFR fell by 31 +/- 9 and 47 +/- 10%, respectively, when RAP was reduced in steps to 70 mmHg. These data suggest that hyperglycemia impairs renal autoregulation and may increase renal blood flow and GFR through a tubuloglomerular feedback mechanism.

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation

2009 ◽  
Vol 296 (6) ◽  
pp. F1334-F1345 ◽  
Author(s):  
Erdmann Seeliger ◽  
Thomas Wronski ◽  
Mechthild Ladwig ◽  
Leszek Dobrowolski ◽  
Torsten Vogel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Mirror Image ◽  
Tubuloglomerular Feedback ◽  
Step Response ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Vascular

Autoregulation of renal blood flow comprises three mechanisms: the myogenic response (MR), the tubuloglomerular feedback (TGF), and a third mechanism (3M). The nature of 3M is unknown; it may be related to hypotensive resetting of autoregulation that probably relies on pressure-dependent stimulation of the renin-angiotensin system (RAS). Thus we used a normotensive angiotensin II clamp in anesthetized rats and studied autoregulation 1) by slow ramp-shaped reductions in renal perfusion pressure (RPP) followed by ramp-shaped RPP restorations and 2) by means of the step response technique: after 30 s of either total or partial suprarenal aortic occlusion, a step increase in RPP was made and the response of renal vascular conductance analyzed to assess the mechanisms' strength and initial direction (vasodilation or constriction). The angiotensin clamp abolished the resetting of autoregulation during ramp-shaped RPP changes. Under control conditions, the initial TGF response was dilatory after total occlusions but constrictive after partial occlusions. The initial 3M response presented a mirror image to the TGF: it was constrictive after total but dilatory after partial occlusions. The angiotensin clamp suppressed the TGF and turned the initial 3M response following total occlusions into dilation. We conclude that 1) pressure-dependent RAS stimulation is a major cause behind hypotensive resetting of autoregulation, 2) TGF sensitivity strongly depends on pressure-dependent changes in RAS activity, 3) the 3M is modulated, but not mediated, by the RAS, and 4) the 3M acts as a counterbalance to the TGF and might possibly be related to the recently described connecting tubule glomerular feedback.

Renal hemodynamics and vascular reactivity in canine DOCA-salt hypertension

1988 ◽  
Vol 255 (4) ◽  
pp. R563-R568
Author(s):  
J. L. Goering ◽  
P. C. Raich ◽  
B. G. Zimmerman
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Control Period ◽  
Indwelling Catheter ◽  
Alpha Adrenoceptor ◽  
Arterial Blood ◽  
Salt Hypertension ◽  
Renal Vascular

Because of the potential role that the kidney may play in deoxycorticosterone acetate (DOCA)-salt hypertension, changes in renal blood flow, renal vascular reactivity, and renal adrenergic vascular tone were followed in the conscious instrumented dog. DOCA-salt was administered daily after obtaining control measurements. Systemic mean arterial blood pressure (MAP) was monitored with an indwelling catheter, renal blood flow (RBF) was measured electromagnetically using an implanted blood flow probe, and drugs were administered intrarenal arterially through an indwelling renal artery catheter. During the first week of DOCA-salt administration MAP increased from 106 +/- 3 to 118 +/- 2 mmHg and at week 2 to 123 +/- 2 mmHg (P less than 0.01). RBF increased from 275 +/- 32 to 336 +/- 34 during week 1 (P less than 0.05) and to 324 +/- 29 ml/min during week 2. The log ED50 of norepinephrine administered intra-arterially decreased from 1.66 +/- 0.114 to 1.48 +/- 0.091 and 1.41 +/- 0.067 ng/ml (P less than 0.05), and of angiotensin II from 2.58 +/- 0.072 to 2.31 +/- 0.09 (P less than 0.05) and 2.38 +/- 0.05 pg/ml, during weeks 1 and 2, respectively. There was, however, no increase in adrenergic vascular tone as determined by the change in RBF obtained with the intra-arterial infusion of alpha-adrenoceptor antagonists. These experiments indicate that RBF is not compromised in canine DOCA-salt hypertension, and renal adrenergic tone is no greater in the hypertensive than in the normotensive control period.

Plasma dopamine in regulation of canine renal blood flow

1988 ◽  
Vol 255 (3) ◽  
pp. R379-R387 ◽  
Author(s):  
D. R. Kapusta ◽  
N. W. Robie
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sch 23390 ◽  
Renal Perfusion ◽  
Receptor Activation ◽  
Renal Autoregulation ◽  
Alpha Adrenoceptor ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Control Infusion

Studies were performed in pentobarbital-anesthetized dogs to determine whether circulating plasma dopamine (DA) is involved in renal blood flow (RBF) regulation. During graded reductions in renal perfusion pressure (RPP), total renal venous (RV) DA content significantly increased at RPPs below the autoregulatory range. The RBF response to decrements in RPP was also examined during control, infusion of DA (1.2 micrograms.kg(-1).min(-1)ia), and after DA receptor blockade by SCH 23390 (30 micrograms/kg iv). During DA infusion, autoregulation was still evident over the same RPPs, although at higher flow rates. At pressures below the autoregulatory range, RBF decreased linearly and the autoregulatory curve merged with control at 50 mmHg. After SCH 23390, autoregulation ceased at a higher RPP than during control, and RBF was significantly less than control rates at pressures of 80 mmHg and below. To elucidate reasons for this latter response, reductions in RPP were repeated before and after administration of both prazosin (0.1 mg/kg iv) and SCH 23390. The results indicated that RBF rates were not different from control at any RPP. Further, prazosin alone did not alter renal autoregulation but significantly increased RBF at RPP below the autoregulatory range. Thus these results indicate that dopamine does not participate in RBF control at pressures above the inflection point for the lowest limit of RBF autoregulation but may be released at lower RPP to act as a vasodilator agent to oppose alpha-adrenoceptor-mediated reductions in RBF. Moreover, tonic DA receptor activation may influence the setting of the lower limit of canine RBF autoregulation.

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.

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.

Alteration of canine renal vascular response to hemorrhage by inhibitors of prostaglandin synthesis

1976 ◽  
Vol 230 (4) ◽  
pp. 940-945 ◽  
Author(s):  
JL Data ◽  
LC Chang ◽  
AS Nies
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Control Period ◽  
Prostaglandin Synthesis ◽  
Hemorrhagic Hypotension ◽  
Renal Cortical Blood Flow ◽  
Renal Vascular ◽  
Inner Cortex ◽  
Equal Thickness ◽  
Total Renal Blood Flow

The involvement of prostaglandins in the redistribution of renal cortical blood flow to inner cortical nephrons during hemorrhagic hypotension was studied in the pentobarbital-anesthetized dog. Total renal blood flow and distribution of renal cortical flow were determined with the radioactive microsphere technique by dividing the cortex into four zones of equal thickness, zone 1 being outermost and zone 4 being juxtamedullary. Two inhibitors of prostaglandin synthesis were used: indomethacin 8 mg/kg and aspirin 100 mg/kg. The inhibitor or the vehicle was given intravenously prior to a control period which was followed by a hemorrhage sufficient to decrease arterial pressure by about one-third. The distribution of cortical flow was determined before hemorrhage, during hemorrhagic hypotension, and after transfusion. In the vehicle-treated dogs, total renal blood flow was well maintained, but flow redistributed to favor the inner cortical nephrons. This vasodilation in the inner cortex was blocked by both inhibitors of prostaglandin synthesis resulting in a decrease in total renal blood flow and relative ischemia of the juxtamedullary nephrons. Salicylate levels required to accomplish blockage of inner cortical vasodilaton were less than 7 mg/100 ml. These studies indicate that prostaglandins are responsible for the decreased vascular resistance of the inner cortical nephrons which results in the redistribution of blood flow during hemorrhage, and when prostaglandin synthesis is blocked, the kidney vasculature constricts during hemorrhage.

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.

Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow

1994 ◽  
Vol 266 (2) ◽  
pp. F275-F282 ◽  
Author(s):  
A. P. Zou ◽  
J. D. Imig ◽  
M. Kaldunski ◽  
P. R. Ortiz de Montellano ◽  
Z. Sui ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Epoxyeicosatrienoic Acids ◽  
Blood Flows ◽  
Renal Perfusion Pressure ◽  
Renal Vascular

The present study evaluated the role of endogenous P-450 metabolites of arachidonic acid (AA) on autoregulation of renal blood flow in rats. Whole kidney and cortical blood flows were well autoregulated when renal perfusion pressure was varied from 150 to 100 mmHg. Infusion of 17-octadecynoic acid (17-ODYA) into the renal artery (33 nmol/min) increased cortical and papillary blood flows by 12.6 +/- 2.5 and 26.5 +/- 4.6%, respectively. After 17-ODYA, autoregulation of whole kidney and cortical blood flows was impaired. Intrarenal infusion of miconazole (8 nmol/min) had no effect on autoregulation of whole kidney, cortical, or papillary blood flows. 17-ODYA (1 microM) inhibited the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) and 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) by renal preglomerular microvessels in vitro by 83.7 +/- 7.4% and 89.0 +/- 4.9%, respectively. Miconazole (1 microM) reduced the formation of EETs by 86.4 +/- 5.7%, but it had no effect on the production of 20-HETE. These results suggest that endogenous P-450 metabolites of AA, particularly 20-HETE, may participate in the autoregulation of renal blood flow.

scholarly journals Impaired autoregulation of renal blood flow in the fawn-hooded rat

1999 ◽  
Vol 276 (1) ◽  
pp. R189-R196 ◽  
Author(s):  
Richard P. E. Van Dokkum ◽  
Magdalena Alonso-Galicia ◽  
Abraham P. Provoost ◽  
Howard J. Jacob ◽  
Richard J. Roman
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Urinary Protein Excretion ◽  
Renal Perfusion Pressure ◽  
Protein Excretion ◽  
Low Blood Pressure ◽  
Renal Vascular

The responses to changes in renal perfusion pressure (RPP) were compared in 12-wk-old fawn-hooded hypertensive (FHH), fawn-hooded low blood pressure (FHL), and August Copenhagen Irish (ACI) rats to determine whether autoregulation of renal blood flow (RBF) is altered in the FHH rat. Mean arterial pressure was significantly higher in conscious, chronically instrumented FHH rats than in FHL rats (121 ± 4 vs. 109 ± 6 mmHg). Baseline arterial pressures measured in ketamine-Inactin-anesthetized rats averaged 147 ± 2 mmHg ( n = 9) in FHH, 132 ± 2 mmHg ( n = 10) in FHL, and 123 ± 4 mmHg ( n = 9) in ACI rats. Baseline RBF was significantly higher in FHH than in FHL and ACI rats and averaged 9.6 ± 0.7, 7.4 ± 0.5, and 7.8 ± 0.9 ml ⋅ min−1 ⋅ g kidney wt−1, respectively. RBF was autoregulated in ACI and FHL but not in FHH rats. Autoregulatory indexes in the range of RPPs from 100 to 150 mmHg averaged 0.96 ± 0.12 in FHH vs. 0.42 ± 0.04 in FHL and 0.30 ± 0.02 in ACI rats. Glomerular filtration rate was 20–30% higher in FHH than in FHL and ACI rats. Elevations in RPP from 100 to 150 mmHg increased urinary protein excretion in FHH rats from 27 ± 2 to 87 ± 3 μg/min, whereas it was not significantly altered in FHL or ACI rats. The percentage of glomeruli exhibiting histological evidence of injury was not significantly different in the three strains of rats. These results indicate that autoregulation of RBF is impaired in FHH rats before the development of glomerulosclerosis and suggest that an abnormality in the control of renal vascular resistance may contribute to the development of proteinuria and renal failure in this strain of rats.

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