Autoregulation of the glomerular filtration rate and the single-nephron glomerular filtration rate despite inhibition of tubuloglomerular feedback in rats chronically volume-expanded by deoxycorticosterone acetate

1990 ◽  
Vol 416 (5) ◽  
pp. 548-553 ◽  
Author(s):  
D. A. H�berle ◽  
B. K�nigbauer ◽  
J. M. Davis ◽  
T. Kawata ◽  
C. Mast ◽  
...  
1986 ◽  
Vol 250 (6) ◽  
pp. F967-F974 ◽  
Author(s):  
U. Boberg ◽  
A. E. Persson

Studies of whole-kidney function and micropuncture measurements in superficial nephrons were performed to investigate the role of the tubuloglomerular feedback (TGF) in the excretion of salt and water in hydropenic and volume-expanded rats of the spontaneously hypertensive Milan strain (MHS). The rats were 3.5-5 and 5-7 wk old, and age-matched animals from the Milan normotensive strain (MNS) served as controls. There was no difference in mean arterial blood pressure (Pa) between the 3.5- to 5-wk-old prehypertensive MHS (MHSp) and MNS rats, but the glomerular filtration rate (GFR) was higher in MHSp than in MNS [1.35 vs. 0.80 ml X min-1 X g kidney wt (KW)-1, P less than 0.01]. The distal single-nephron glomerular filtration rate (SNGFR) was also higher in MHSp than in MNS (28.6 vs. 20.2 nl X min-1 X g KW-1, P less than 0.05). TGF was determined from both stop-flow pressure response and proximal and distal SNGFR. It was found that MHSp exhibited essentially no TGF response. During development of hypertension 5- to 7-wk-old MHS (MHSd) had a higher Pa than MNS (120 vs. 98 mmHg, P less than 0.01). Normally GFR and SNGFR increase with age, and such was the case with MNS (0.8 to 1.02 ml X min-1 X g KW-1 and 20.2 to 23.4 nl X min-1 X g KW-1), but in MHSd there was a decrease in both GFR and SNGFR with age (1.35 to 1.10 ml X min-1 X g KW-1 and 28.3 to 18.3 nl X min-1 X g KW-1).(ABSTRACT TRUNCATED AT 250 WORDS)


1979 ◽  
Vol 237 (1) ◽  
pp. F63-F74 ◽  
Author(s):  
L. C. Moore ◽  
J. Schnermann ◽  
S. Yarimizu

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.


1985 ◽  
Vol 248 (5) ◽  
pp. F688-F697 ◽  
Author(s):  
G. A. Tanner

The effects of 1 day of single nephron, unilateral ureteral (UUO), and bilateral ureteral (BUO) obstruction on tubuloglomerular feedback were studied in anesthetized rats. Stop-flow pressure (SFP) was measured as an index of glomerular capillary pressure before, during, and after loop of Henle microperfusion. Tubuloglomerular feedback (delta SFP) showed an increased sensitivity to low loop perfusion rates and an increased maximal response after 1 day of single nephron obstruction or relief of UUO. Tubuloglomerular feedback was not significantly different from normal after release of BUO. Whole kidney glomerular filtration rate (GFR) was about 10% of normal after release of ureteral obstruction, and single nephron glomerular filtration rate (SNGFR) averaged one-third of normal. Paired measurements of SNGFR from proximal and distal tubules revealed no significant differences in control or in BUO kidneys, but a significant proximal-distal SNGFR difference was observed after UUO. The results suggest that tubuloglomerular feedback does not significantly contribute to the low GFR after release of BUO; after release of UUO, approximately one-fourth of the fall in GFR may be due to activation of the feedback mechanism.


1985 ◽  
Vol 249 (4) ◽  
pp. F524-F531 ◽  
Author(s):  
U. Boberg ◽  
A. E. Persson

Interstitial hydrostatic and oncotic pressures are believed to influence the sensitivity of the tubuloglomerular feedback (TGF) control. To further investigate this hypothesis, three groups of experiments with elevated renal venous pressure (Prv) were conducted. We investigated 1) the stop-flow pressure (Psf) feedback response; 2) urine flow rate, glomerular filtration rate (GFR), subcapsular interstitial hydrostatic pressure (Psc), and interstitial oncotic pressure (pi int); and 3) the proximal-distal single nephron glomerular filtration rate (SNGFR). The results showed that the Psf feedback response was unaffected by Prv elevation. Psc increased from 0.5 to 3.5 mmHg and pi int increased from 2.1 to 5.8 mmHg; thus, no change in net interstitial pressure (Psc - pi int) was found during elevated Prv. There was a significant proximal-distal SNGFR difference during both control and elevated Prv (8.0 and 6.3 nl/min, respectively). A 20% reduction in total GFR and SNGFR was observed at increased Prv. In separate experiments using the same protocol, a 5% body wt/h volume expansion with saline was induced before Prv was elevated. During volume expansion, TGF sensitivity declined and net interstitial pressure increased, both of which were normalized by increasing Prv. The results show that the TGF sensitivity is normal during elevated Prv to 20 mmHg and that the increase in Psc during this condition is counter-balanced by an increase in pi int. In addition, the decrease in GFR and SNGFR during increased Prv cannot be explained by a change in TGF activity. However, these findings indicate that both interstitial hydrostatic and oncotic pressures may influence the resetting of the TGF sensitivity.


1986 ◽  
Vol 251 (1) ◽  
pp. F25-F33 ◽  
Author(s):  
A. Goransson ◽  
M. Sjoquist ◽  
H. R. Ulfendahl

The influence of the renin-angiotensin system on whole-kidney and regional single-nephron function was studied in anesthetized Munich-Wistar rats by use of a converting enzyme inhibitor (CEI), captopril (3 mg . h-1 . kg-1 body wt-1). Single-nephron glomerular filtration rate (SNGFR) was measured in superficial (S) and juxtamedullary (JM) nephrons by a micropuncture technique that blocked tubuloglomerular feedback (TGF) activity. Hydrostatic free-flow pressure (FFP) measurements were conducted in S proximal tubules, in JM loops of Henle, and in papillary vasa recta. Glomerular filtration rate (GFR) and urinary electrolyte excretion were measured in the contralateral kidney. In the control situation SNGFR of S nephrons was 35.4 +/- 2.24 nl . min-1 . g kidney wt-1 and of JM nephrons was 75.0 +/- 9.41 nl . min-1 . g-1 kidney wt-1. Thus it was more than twice as high in JM as in S nephrons when the TGF activity was blocked. In this situation administration of CEI had no additional effect on either S or JM nephrons. However, administration of CEI resulted in a significant increase in whole-kidney GFR by 25% (P less than 0.05) and in urine flow rate by 60% (P less than 0.001) under free-flow conditions. Further, intratubular FFP increased significantly in JM nephrons by an average of 2.9 +/- 0.52 mmHg (P less than 0.001), indicating an increase in tubular urine flow in JM nephrons, whereas S nephrons were unaffected. These results suggest an active preglomerular vasoconstriction in JM nephrons under normal free-flow conditions. This seems to be mediated by TGF and modulated by angiotensin II.


1990 ◽  
Vol 259 (5) ◽  
pp. F739-F746 ◽  
Author(s):  
S. A. Brown ◽  
L. G. Navar

It has been suggested that the tubuloglomerular feedback (TGF) system is responsible for renal vasodilation during systemic infusion of amino acid solutions. We evaluated the effect of intravenous administration of amino acids (serine, alanine, proline, and glycine; total dose of 0.075 mmol of amino acids.kg body wt-1.min-1) on whole kidney and single-nephron hemodynamics in pentobarbital sodium-anesthetized dogs. At spontaneous renal arterial pressure (RAP; 125.4 +/- 4.7 mmHg), measurements of single-nephron function obtained during tubular blockade, stop-flow pressure (SFP; 48.2 +/- 2.0 vs. 58.9 +/- 2.3 mmHg, P less than 0.01), and proximally determined single-nephron glomerular filtration rate (SNGFR-TPC; 73.9 +/- 7.0 vs. 93.4 +/- 7.6 nl/min, P less than 0.01) increased in parallel to the increases of outer cortical blood flow (OCBF; 15.4 +/- 1.1 vs. 19.1 +/- 1.5 units, P less than 0.05), renal blood flow (RBF; 4.60 +/- 0.18 vs. 5.73 +/- 0.22 ml.min-1.g kidney wt-1, P less than 0.01), and glomerular filtration rate (GFR; 0.885 +/- 0.034 vs. 1.116 +/- 0.034 ml.min-1.g kidney wt-1, P less than 0.01). Free-flow tubular fluid-to-plasma inulin ratios, determined from late proximal recollections during saline (control) and amino acid infusions failed to provide evidence for altered proximal reabsorption rate (1.63 +/- 0.12 vs. 1.58 +/- 0.17 during amino acids, NS). At reduced RAP (92.6 +/- 1.9 mmHg), where it is presumed that TGF-mediated vasodilation is already near maximal, the vasodilatory response to amino acid infusion was intact and single-nephron parameters measured during tubular blockade increased to the same extent as OCBF, RBF, and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 22 (11) ◽  
pp. 5819
Author(s):  
Rui Hu ◽  
Anita Layton

At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney function and may contribute to the development of chronic kidney disease. The goal of this study is to analyze how kidney function is altered in patients with diabetes and the renal effects of an anti-hyperglyceamic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish that goal, we have developed a computational model of kidney function in a patient with diabetes and conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Simulation results indicate that diabetes-induced hyperfiltration and tubular hypertrophy enhances Na+ transport, especially along the proximal tubules and thick ascending limbs. These simulations suggest that SGLT2 inhibition may attenuate glomerular hyperfiltration by limiting Na+-glucose transport, raising luminal [Cl−] at the macula densa, restoring the tubuloglomerular feedback signal, thereby reducing single-nephron glomerular filtration rate.


1984 ◽  
Vol 246 (1) ◽  
pp. F12-F20 ◽  
Author(s):  
J. R. Dilley ◽  
C. T. Stier ◽  
W. J. Arendshorst

Clearance and micropuncture studies were conducted on 6-wk-old spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain and normotensive Wistar-Kyoto rats (WKY) under euvolemic conditions. Mean arterial pressure in SHR was elevated by 18 mmHg and their kidneys were vasoconstricted with reduced blood flow; resistances in preglomerular vessels and efferent arterioles were elevated 2.8 and 2 times, respectively, above WKY values. Whole kidney glomerular filtration rate (GFR) and single nephron glomerular filtration rate (SNGFR), based on fluid collection from either proximal or distal convolutions, were 25-30% lower in SHR. Fractional reabsorptions of fluid load by the proximal convoluted tubule (43%) and by the loop of Henle (52-55%) were similar in both groups. Accordingly, SHR exhibited less fluid delivery from the proximal convolution (8 vs. 12 nl/min) and to the distal convolution (3 vs. 5 nl/min). Glomerular dynamics in hypertensive and normotensive strains were characterized by filtration pressure disequilibrium. Estimated glomerular capillary pressure and mean effective ultrafiltration pressure were similar in SHR and WKY. SHR had a lower glomerular ultrafiltration coefficient than WKY (0.011 vs. 0.016 nl X s-1 X mmHg-1), which, combined with a lower glomerular plasma flow (41 vs. 73 nl/min), quantitatively accounted for the lower SNGFR in 6-wk-old SHR. These findings document important differences in renal function in young SHR compared with WKY that may participate in the development of hypertension.


1981 ◽  
Vol 241 (6) ◽  
pp. F612-F617
Author(s):  
E. J. Braun ◽  
D. R. Roy ◽  
R. L. Jamison

A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.


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