scholarly journals Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

2004 ◽  
Vol 287 (1) ◽  
pp. R58-R68 ◽  
Author(s):  
Elisabete A. Dos Santos ◽  
Annette J. Dahly-Vernon ◽  
Kimberly M. Hoagland ◽  
Richard J. Roman
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Brush Border ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Inhibitory Effects ◽  
Sodium Hydrogen Exchanger ◽  
Pressure Natriuresis ◽  
Cytochrome P 450 ◽  
Filtered Load

This study examined the effects of chronic blockade of the renal formation of epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid with 1-aminobenzotriazole (ABT; 50 mg·kg−1· day−1 ip for 5 days) on pressure natriuresis and the inhibitory effects of elevations in renal perfusion pressure (RPP) on Na+-K+-ATPase activity and the distribution of the sodium/hydrogen exchanger (NHE)-3 in the proximal tubule of rats. In control rats ( n = 15), sodium excretion rose from 2.3 ± 0.4 to 19.4 ± 1.8 μeq·min−1·g kidney weight−1 when RPP was increased from 114 ± 1 to 156 ± 2 mmHg. Fractional excretion of lithium rose from 28 ± 3 to 43 ± 3% of the filtered load. Chronic treatment of the rats with ABT for 5 days ( n = 8) blunted the natriuretic response to elevations in RPP by 75% and attenuated the increase in fractional excretion of lithium by 45%. In vehicle-treated rats, renal Na+-K+-ATPase activity fell from 31 ± 5 to 19 ± 2 μmol Pi·mg protein−1·h−1 and NHE-3 protein was internalized from the brush border of the proximal tubule after an elevation in RPP. In contrast, Na+-K+-ATPase activity and the distribution of NHE-3 protein remained unaltered in rats treated with ABT. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to pressure natriuresis by inhibiting Na+-K+-ATPase activity and promoting internalization of NHE-3 protein from the brush border of the proximal tubule.

Renal interstitial hydrostatic pressure and pressure natriuresis in pregnant rats

2000 ◽  
Vol 279 (2) ◽  
pp. F353-F357 ◽  
Author(s):  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium ◽  
Pressure Natriuresis

The objective of this study was to test the hypothesis that a decrease in renal interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9), midterm pregnant (MP; 12–14 days after conception; n = 10), and late-term pregnant (LP; 18–21 days after conception; n = 12) female Sprague-Dawley rats at two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP level, RIHP was 5.9 ± 0.3 mmHg for NP, 3.4 ± 0.4 mmHg for MP ( P < 0.05 vs. NP), and 2.9 ± 0.1 mmHg for LP ( P < 0.05 vs. NP) rats. The increase in RPP from 99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all groups; however, the increases in fractional excretion of sodium (ΔFENa), urine flow rate (ΔV), and ΔRIHP were significantly greater ( P < 0.05) in NP compared with both MP and LP rats. ΔFENa, ΔV, and ΔRIHP were 2.06 ± 0.28%, 81.44 ± 14.10 μl/min, and 3.0 ± 0.5 mmHg for NP; 0.67 ± 0.13%, 28.03 ± 5.28 μl/min, and 0.5 ± 0.2 mmHg for MP; and 0.48 ± 0.12%, 18.14 ± 4.70 μl/min, and 0.4 ± 0.1 mmHg for LP rats. In conclusion, RIHP is significantly lower in pregnant compared with nonpregnant rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP in response to an increase in RPP is blunted. These changes in RIHP may play an important role in the blunted pressure natriuresis and contribute to the conservation of sodium and water that is critical for fetal growth and development during normal pregnancy.

Renal interstitial hydrostatic pressure and PGE2 in pressure natriuresis

1991 ◽  
Vol 260 (5) ◽  
pp. F643-F649 ◽  
Author(s):  
J. M. Gonzalez-Campoy ◽  
C. Long ◽  
D. Roberts ◽  
T. J. Berndt ◽  
J. C. Romero ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Blood Flows ◽  
Renal Perfusion Pressure ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis ◽  
Indomethacin Treatment

The present study tested the hypothesis that the presence of renal prostaglandin E2 (PGE2) is necessary for full natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during increased renal perfusion pressure (RPP). In control untreated pentobarbital-anesthetized dogs (n = 7), fractional excretion of sodium (FENa) was 1.17 +/- 0.48, 1.07 +/- 0.24, and 2.69 +/- 0.57% at RPP of 90, 122, and 148 mmHg, respectively. These changes in FENa were associated with effective renal blood flows (ERBF) of 1.43 +/- 0.20, 1.49 +/- 0.23, and 1.99 +/- 0.40 ml.min-1.g kidney wt-1, respectively. Similarly, glomerular filtration rate (GFR) was 0.53 +/- 0.10, 0.71 +/- 0.10, and 0.72 +/- 0.14 ml.min-1.g kidney wt-1, respectively. Treatment with indomethacin, a cyclooxygenase inhibitor, significantly lowered FENa to 0.45 +/- 0.13, 0.77 +/- 0.21, and 1.19 +/- 0.59% at RPP of 91, 121, and 146 mmHg, respectively. Additionally, indomethacin treatment lowered ERBF (0.51 +/- 0.15, 0.52 +/- 0.10, and 0.85 +/- 0.21 ml.min-1.g kidney wt-1) and GFR (0.28 +/- 0.09, 0.34 +/- 0.09, and 0.47 +/- 0.09 ml.min-1.g kidney wt-1) at low, middle, and high RPP, respectively. PGE2 replacement (n = 6) into renal artery at 0.01 microgram.min-1.kg body wt-1 returned FENa, ERBF, and GFR to control levels over the same range of RPP, whereas prostacyclin (PGI2) infusion (n = 7) at the same dose did not. RIHP was 4.2 +/- 1.2, 4.2 + 0.5, and 7.5 +/- 1.7 mmHg with increasing RPP in control untreated group and increased to similar levels with indomethacin treatment and during PGE2 or PGI2 replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of metabolic acidosis on glucose reabsorption in rats with acute hyperglycemia

1990 ◽  
Vol 68 (1) ◽  
pp. 79-83 ◽  
Author(s):  
P. O. Magner ◽  
M. L. Halperin
Keyword(s):  
Proximal Tubule ◽  
Fractional Excretion ◽  
Electrochemical Gradient ◽  
Osmotic Diuresis ◽  
Acute Hyperglycemia ◽  
Luminal Membrane ◽  
Glucose Reabsorption ◽  
Other Substances ◽  
Hyperglycemic Hyperosmolar Nonketotic Coma ◽  
Filtered Load

The rate of reabsorption of glucose in the kidney is a factor to consider with respect to the degree of hyperglycemia in poorly controlled diabetics. The rate of reabsorption of glucose in the proximal tubule is driven by the electrochemical gradient for sodium across the luminal membrane. This gradient in the proximal tubule is also used to reabsorb a number of other substances, quantitatively the most important being bicarbonate. We wished to explore the hypothesis that acidosis, by reducing the filtered load of bicarbonate and therefore the reabsorption of bicarbonate in the proximal tubule, might permit an increased rate of reabsorption of glucose. Hyperglycemia was induced in rats by the infusion of hypertonic glucose. Reabsorption of glucose was measured by clearance methods and factored for glomerular filtration rate (GFR), which has a direct effect on the reabsorption of glucose. The reabsorption of glucose was increased in the kidney when the reabsorption of bicarbonate in the proximal tubule was decreased by either HCl-induced acidosis or the administration of a carbonic anhydrase inhibitor. This effect was independent of a change in GFR and the fractional excretion of Na, factors that may also lead to changes in the reabsorption of glucose by the kidney.Key words: diabetes mellitus, hyperglycemic hyperosmolar nonketotic coma, diabetic ketoacidosis, proximal convoluted tubule, hyperglycemia, glucosuria, osmotic diuresis.

Proximal tubular reabsorption and Na-K-ATPase activity in remnant kidney of young rats

1986 ◽  
Vol 251 (4) ◽  
pp. F588-F593 ◽  
Author(s):  
G. Celsi ◽  
L. Larsson ◽  
A. Aperia
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Basolateral Membrane ◽  
Close Correlation ◽  
Sodium Reabsorption ◽  
Membrane Area ◽  
Single Nephron ◽  
Proximal Tubular ◽  
Filtered Load ◽  
Remnant Kidney

In rats unilaterally nephrectomized (NX) in infancy, the compensatory growth of the remnant kidney is due first to hypertrophy and hyperplasia, but after 2 wk only to hyperplasia. We studied proximal tubular adaptation (reabsorption, Na-K-ATPase activity, length, and basolateral membrane area) 2 and 8 wk after NX. The rats were NX at 5 days of age. The size of remnant kidney obtained from uninephrectomized rats was 125% at 2 wk and 179% at 8 wk relative to the appropriate time-related controls. Single-nephron glomerular filtration rate in the uninephrectomized group was doubled relative to controls, whereas fractional reabsorption by the proximal tubule was unchanged. Na-K-ATPase activity per millimeter of proximal convoluted tubule (PCT) was significantly increased in the uninephrectomized group relative to controls at 2 but not 8 wk. The area of the basolateral cell membrane per millimeter PCT was unchanged at both 2 and 8 wk, which suggests that the density of enzyme units inserted in the membrane was increased at 2 but not at 8 wk. PCT length was increased at 8 but not at 2 wk. There was a close correlation between total PCT Na-K-ATPase activity and filtered sodium (r = 0.999) and between total PCT Na-K-ATPase activity and PCT sodium reabsorption (r = 0.998). We conclude that the proximal tubule can adapt to an increased filtered load by increasing the density of transporting units or by increasing the tubular length. The latter stage may be attained only in young growing animals.

Effects of renal artery pressure on interstitial pressure and Na excretion during renal vasodilation

1988 ◽  
Vol 255 (5) ◽  
pp. F828-F833 ◽  
Author(s):  
J. P. Granger ◽  
J. W. Scott
Keyword(s):  
Perfusion Pressure ◽  
Marked Effect ◽  
Excretion Rate ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Interstitial Pressure ◽  
Pressure Natriuresis ◽  
The Relationship

Renal vasodilation has a marked effect on the pressure-natriuresis relationship. The purpose of this study was to determine the role of renal interstitial hydrostatic pressure (RIHP) in mediating the effect of renal perfusion pressure (RPP) on urinary sodium excretion rate (UNaV) in control and vasodilated kidneys. The effects of RPP on UNaV and RIHP were determined in dogs under control conditions and during renal vasodilation with acetylcholine (Ach, 2.0 micrograms.kg-1.min-1) or secretin (SEC, 0.025 micrograms.kg-1.min-1). Decreases in RPP in control kidneys from 130 to 60 mmHg decreased UNaV from 2.9 +/- 0.1 to 0.6 +/- 0.3 microeq/min and fractional excretion of Na (FENa) from 0.15 +/- 0.08 to 0.06 +/- 0.04%. These changes were associated with significant reductions in RIHP (8.9 +/- 0.6 to 5.6 +/- 1.2 mmHg). In Ach-vasodilated kidneys, reductions in RPP from 130 to 60 mmHg decreased UNaV from 149.8 +/- 52.4 to 0.2 +/- 0.1 microeq/min and FENa from 3.42 +/- 1.18 to 0.012 +/- 0.01%. RIHP decreased from 17.8 +/- 3.4 to 8.4 +/- 1.3 mmHg, despite autoregulation of RBF. Renal vasodilation with SEC, which did not affect RIHP, had only a small effect on the relationship between RPP and UNaV. These data suggest that RIHP may be playing an important role in mediating the effect of RPP on UNaV.

scholarly journals Angiotensin II stimulates vesicular H+-ATPase in rat proximal tubular cells

1998 ◽  
Vol 95 (16) ◽  
pp. 9665-9668 ◽  
Author(s):  
Carsten A. Wagner ◽  
Gerhard Giebisch ◽  
Florian Lang ◽  
John P. Geibel
Keyword(s):  
Angiotensin Ii ◽  
Atpase Activity ◽  
Proximal Tubule ◽  
Brush Border ◽  
Channel Blocker ◽  
Proximal Tubular Cells ◽  
Proton Extrusion ◽  
Tubular Cells ◽  
Ion Secretion ◽  
Proximal Tubular

Two mechanisms of H+ ion secretion in the proximal tubule that mediate bicarbonate reabsorption have been identified: the brush border Na/H exchanger and electrogenic H+ ion secretion. Angiotensin II (AII) has been shown to be a regulator of the luminal Na+/H+ exchanger and the basolateral Na+/HCO3− cotransporter. In the present study, we examined the effects of AII on H+-ATPase activity in isolated proximal tubule fragments. H+-ATPase activity was assessed by monitoring intracellular pH after Na+ removal from the bath. In addition, we investigated the effects on pH recovery of the proton pump inhibitor bafilomycin A1, removal of Cl−, and of colchicine. pH was continuously measured with the pH-sensitive fluorescent dye 2′, 7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Recovery of cell pH was observed in the absence of external Na+ and was significantly accelerated by AII. The AII-stimulated pH recovery was completely abolished by bafilomycin A1, by removal of Cl−, by NPPB [5-nitro-2-(3-phenylpropylamino)-benzoate; a potent Cl− channel blocker], and by colchicine. We conclude from these studies that AII stimulates proton extrusion via H+-ATPase by a Cl−-dependent process involving brush border insertion of vesicles. This process may contribute to up-regulation of HCO3− reabsorption along the proximal tubule when tubules are exposed to AII.

scholarly journals Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

2014 ◽  
Vol 307 (11) ◽  
pp. F1249-F1262 ◽  
Author(s):  
Jens Christian Brasen ◽  
James L. Burford ◽  
Alicia A. McDonough ◽  
Niels-Henrik Holstein-Rathlou ◽  
Janos Peti-Peterdi
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Brush Border ◽  
Renal Proximal Tubule ◽  
Kidney Cortex ◽  
Proximal Tubule Cell ◽  
Rat Kidney Cortex ◽  
Pressure Natriuresis ◽  
Local Ph

The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.

scholarly journals The cytochrome P-450 inhibitor cobalt chloride prevents inhibition of renal Na,K-ATPase and redistribution of apical NHE-3 during acute hypertension.

1998 ◽  
Vol 9 (4) ◽  
pp. 531-537 ◽  
Author(s):  
Y B Zhang ◽  
C E Magyar ◽  
N H Holstein-Rathlou ◽  
A A McDonough
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Urine Output ◽  
Cobalt Chloride ◽  
Renal Cortex ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Acute Hypertension ◽  
Arachidonate Metabolites ◽  
Cytochrome P 450

Acute systolic arterial hypertension provokes a rapid decrease in proximal tubule sodium reabsorption and diuresis associated with inhibition of renal cortex Na,K-ATPase activity and redistribution of apical membrane Na/H exchanger (NHE-3) to heavier density membranes containing markers of intermicrovillar cleft and endosomes. Because cytochrome P-450-dependent arachidonate metabolites participate in the regulation of renal sodium transport and BP, this study tested the hypothesis that these renal responses to acute hypertension would be prevented if cytochrome P-450 metabolism were inhibited by cobalt chloride (CoCl2). Four groups of rats (n = 4 to 5) were studied: (1) sham-operated; (2) 50 mg of CoCl2/kg subcutaneously for 2 d; (3) acute hypertension by constricting arteries for 5 min; and (4) acute hypertension after CoCl2 treatment as in group 3. Renal cortex was analyzed after sorbitol density gradient fractionation. CoCl2 treatment alone did not significantly affect the rate of urine output, endogenous lithium clearance (an inverse measure of proximal tubule sodium reabsorption), maximal activity of Na,K-ATPase, or subcellular distribution of NHE-3-containing membranes. In non-CoCl2-treated animals, acute hypertension provoked a three- to fourfold increase in urine output and endogenous lithium clearance, 33% inhibition of renal cortex Na,K-ATPase activity, and redistribution of NHE-3 out of the apical membrane peak. In CoCl2-treated animals, acute urine output and endogenous lithium clearance increased only twofold during acute hypertension, there was no inhibition of Na,K-ATPase activity, and there was no redistribution of NHE-3 immunoreactivity to higher density membranes. These findings demonstrate that CoCl2 treatment both attenuates the inhibition of proximal tubule sodium reabsorption and diuresis and abolishes Na,K-ATPase inhibition and NHE-3 redistribution during acute hypertension, evidence that these responses may be mediated by cytochrome P-450 arachidonate metabolites.

Effect of renal decapsulation on renal interstitial hydrostatic pressure and natriuresis

1989 ◽  
Vol 257 (1) ◽  
pp. R44-R48 ◽  
Author(s):  
A. A. Khraibi ◽  
F. G. Knox
Keyword(s):  
Hydrostatic Pressure ◽  
Volume Expansion ◽  
Wistar Rats ◽  
Control Period ◽  
Fractional Excretion ◽  
Wistar Rat ◽  
Renal Perfusion ◽  
Fractional Excretion Of Sodium ◽  
Male Wistar Rats ◽  
Pressure Natriuresis

The objective of this study was to investigate the possible causal role of renal interstitial hydrostatic pressure (RIHP) in the natriuretic and diuretic responses of the Wistar rat. The relationship between renal perfusion pressure (RPP), RIHP, and fractional excretion of sodium (FENa) was established in the acutely decapsulated kidney and the contralateral control kidney of the same rat. The renal response to acute saline volume expansion was also studied in control and decapsulated kidney. When RPP was allowed to increase from 100 +/- 1.2 to 123 +/- 1.3 mmHg in male Wistar rats (n = 10), RIHP and FENa increased significantly from 3.3 +/- 0.4 mmHg and 0.57 +/- 0.15% to 4.3 +/- 0.4 mmHg and 1.77 +/- 0.41% in the decapsulated kidney and from 4.1 +/- 0.4 mmHg and 0.86 +/- 0.17% to 6.9 +/- 0.5 mmHg and 2.56 +/- 0.38% in control kidney. During saline volume expansion, RIHP and FENa increased significantly from 6.3 +/- 0.5 mmHg and 1.30 +/- 0.43% to 9.8 +/- 0.5 mmHg and 7.53 +/- 0.88% in the decapsulated kidney. In the control kidney, RIHP and FENa were 8.3 +/- 0.6 mmHg and 1.81 +/- 0.35% during control period and increased significantly to 12.7 +/- 0.4 mmHg and 9.31 +/- 0.50% during acute saline volume expansion. We conclude that the renal capsule is essential for the full increase in RIHP and for the full expression of the natriuretic and diuretic responses of pressure natriuresis and acute volume expansion of Wistar rats.

scholarly journals Dipeptidyl peptidase IV inhibition downregulates Na+-H+exchanger NHE3 in rat renal proximal tubule

2008 ◽  
Vol 294 (2) ◽  
pp. F414-F422 ◽  
Author(s):  
Adriana Castello Costa Girardi ◽  
Lívia Emy Fukuda ◽  
Luciana Venturini Rossoni ◽  
Gerhard Malnic ◽  
Nancy Amaral Rebouças
Keyword(s):  
Proximal Tubule ◽  
Brush Border ◽  
Membrane Vesicles ◽  
Dipeptidyl Peptidase ◽  
Renal Proximal Tubule ◽  
Dipeptidyl Peptidase Iv ◽  
Rat Renal Proximal Tubule ◽  
Sodium Hydrogen Exchanger ◽  
Male Wistar Rats

In the microvillar microdomain of the kidney brush border, sodium hydrogen exchanger type 3 (NHE3) exists in physical complexes with the serine protease dipeptidyl peptidase IV (DPPIV). The purpose of this study was to explore the functional relationship between NHE3 and DPPIV in the intact proximal tubule in vivo. To this end, male Wistar rats were treated with an injection of the reversible DPPIV inhibitor Lys [Z(NO2)]-pyrrolidide (I40; 60 mg·kg−1·day−1ip) for 7 days. Rats injected with equal amounts of the noninhibitory compound Lys[Z(NO2)]-OH served as controls. Na+-H+exchange activity in isolated microvillar membrane vesicles was 45 ± 5% decreased in rats treated with I40. Membrane fractionation studies using isopycnic centrifugation revealed that I40 provoked redistribution of NHE3 along with a small fraction of DPPIV from the apical enriched microvillar membranes to the intermicrovillar microdomain of the brush border. I40 significantly increased urine output (67 ± 9%; P < 0.01), fractional sodium excretion (63 ± 7%; P < 0.01), as well as lithium clearance (81 ± 9%; P < 0.01), an index of end-proximal tubule delivery. Although not significant, a tendency toward decreased blood pressure and plasma pH/HCO3−was noted in I40-treated rats. These findings indicate that inhibition of DPPIV catalytic activity is associated with inhibition of NHE3-mediated NaHCO3reabsorption in rat renal proximal tubule. Inhibition of apical Na+-H+exchange is due to reduced abundance of NHE3 protein in the microvillar microdomain of the kidney brush border. Moreover, this study demonstrates a physiologically significant interaction between NHE3 and DPPIV in the intact proximal tubule in vivo.

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