Proximal and distal tubular activity in chronically catheterized fetal sheep compared with the adult

1988 ◽  
Vol 66 (6) ◽  
pp. 697-702 ◽  
Author(s):  
Eugenie R. Lumbers ◽  
Karen J. Hill ◽  
Victoria J. Bennett

Renal function was studied in unanaesthetized fetal sheep aged 112–120 and 126–132 days and in adult nonpregnant ewes. The clearance of lithium was used to measure proximal and distal fractional sodium reabsorption. In five nonpregnant adult sheep, 80.6 ± 1.7% (SE) of the filtered sodium load was reabsorbed proximaily and 18.2 ± 1.53% distally. This was different from all groups of fetal sheep (p < 0.001). In younger fetuses, proximal fractional sodium reabsorption was less (51.3 ± 2.3% (SE), p < 0.05) and distal fractional sodium reabsorption greater (42.4 ± 2.3% (SE), p < 0.05) than older fetuses (126–132 days old) in which 61.4 ± 2.4% (SE) was reabsorbed proximaily and 33.6 ± 2.5% (SE) distally. In another group of fetuses aged 125–137 days, in which proximal tubular sodium reabsorption was measured after distal tubular blockade, proximal fractional sodium reabsorption was 57.8 ± 2.95% (SE) and distal fractional sodium reabsorption, 38.7 ± 2.64% (SE). In adult sheep there was no relationship between distal tubular sodium reabsorption and glomerular filtration rate, i.e., proximal tubular function was responsible for glomerulotubular balance. However, in the fetuses, both proximal and distal tubular sodium reabsorption contributed to glomerulotubular balance. Thus in fetal life, the proximal tubule participates to a lesser extent in reabsorbing the filtered sodium load possibly because its function is suppressed by its relatively "volume-expanded" state or because it is functionally immature. Therefore, a greater proportion is reabsorbed distally and the distal nephron participates under physiological conditions in glomerulotubular balance.

1975 ◽  
Vol 228 (5) ◽  
pp. 1403-1408 ◽  
Author(s):  
LI Kleinman

The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.


1989 ◽  
Vol 6 (7) ◽  
pp. 614-620 ◽  
Author(s):  
J.-C. Mbanya ◽  
T. H. Thomas ◽  
R. Taylor ◽  
K. G. M. M. Alberti ◽  
R. Wilkinson

1985 ◽  
Vol 249 (2) ◽  
pp. F299-F307 ◽  
Author(s):  
M. E. Olsen ◽  
J. E. Hall ◽  
J. P. Montani ◽  
A. C. Guyton ◽  
H. G. Langford ◽  
...  

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)


2005 ◽  
Vol 289 (4) ◽  
pp. R1099-R1106 ◽  
Author(s):  
Amanda C. Boyce ◽  
Karen J. Gibson ◽  
E. Marelyn Wintour ◽  
Irene Koukoulas ◽  
Eugenie R. Lumbers

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 ± 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses ( P < 0.05), and renal angiotensinogen mRNA levels were ∼2.6-fold higher ( P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed ( P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were ∼two-fold higher throughout infusion ( P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 ± 6.5 to 53.7 ± 10.2%), did not return to control levels (36.1 ± 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 ± 25 to 261 ± 75 μmol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.


1989 ◽  
Vol 257 (2) ◽  
pp. F237-F242 ◽  
Author(s):  
Y. Kinoshita ◽  
J. C. Romero ◽  
F. G. Knox

The effect of prostaglandins (PGs) on proximal sodium reabsorption has not been fully defined. The objective of the present study was to determine the response of proximal tubular sodium reabsorption to infusions of arachidonic acid and specific PGs into the renal interstitium in rats. Renal interstitial infusions of arachidonic acid as well as the individual PGs, I2, E2, and F2 alpha, were employed to elevate the concentration of these PGs in the kidney. Infusion of 10(-4) M arachidonic acid elicited a marked increase of urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2) from 260.1 +/- 52.7 to 507.4 +/- 129.5 pg/min (P less than 0.05) and a smaller increase of PGE2 from 18.4 +/- 11.2 to 25.9 +/- 10.9 pg/min (P less than 0.05). When micropuncture samples were obtained from superficial late proximal tubules, infusion of arachidonic acid increased the fractional delivery of sodium (FDNa) from 47.8 +/- 5.9 to 58.3 +/- 4.6% (n = 6, P less than 0.01). In the presence of indomethacin, arachidonic acid failed to augment FDNa. Infusion of 10(-5) M PGI2 also increased FDNa from 51.4 +/- 3.4 to 64.0 +/- 4.4% (n = 10, P less than 0.01). PGF2 alpha did not change FDNa and PGE2 decreased it from 53.1 +/- 5.4 to 37.4 +/- 3.3% (n = 8, P less than 0.01). In summary, the present study demonstrates that renal interstitial infusion of arachidonic acid decreases sodium reabsorption by the superficial proximal tubules possibly through the stimulation of PGI2 production.


1989 ◽  
Vol 256 (5) ◽  
pp. F942-F947 ◽  
Author(s):  
K. U. Eckardt ◽  
A. Kurtz ◽  
C. Bauer

Regulation of renal erythropoietin (EPO) production is based on an intrarenal oxygen sensor. Whereas the sensitivity of this oxygen sensor to variations in renal oxygen supply is well established, the influence of changes in renal oxygen consumption has not yet been elucidated. Diuretic drugs, which inhibit active sodium reabsorption, reduce tubular oxygen consumption. We therefore investigated the effects of acetazolamide, furosemide, hydrochlorothiazide, and amiloride, known to preferentially inhibit sodium reabsorption at different segments of the nephron, on hypoxia-induced EPO formation in mice. Those drugs that are considered to act mainly in the loop of Henle, distal tubule, and collecting duct (furosemide, hydrochlorothiazide, and amiloride) did not impair EPO formation. Acetazolamide on the other hand, which is thought to act predominantly at the proximal tubular site, significantly reduced EPO formation in response to normobaric hypoxia (8 and 14% O2) and functional anemia (0.1% carbon monoxide). This inhibitory effect of acetazolamide was dose dependent and correlated with the natriuresis induced. It appeared not to depend on the metabolic acidosis induced by the drug, since the simultaneous administration of sodium bicarbonate, which restored standard bicarbonate levels to normal, did not diminish the inhibitory effect of acetazolamide on EPO production. In conclusion the data suggest that the regulation of EPO production is likely to be related to proximal tubular function.


1980 ◽  
Vol 14 (8) ◽  
pp. 989-989 ◽  
Author(s):  
W R Allen ◽  
B H Brouhard ◽  
R E Lynch

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