A micropuncture study of renal lithium reabsorption: effects of amiloride and furosemide

Shirley, DG; Walter, S. J.; Sampson, B.

doi:10.1152/ajprenal.1992.263.6.f1128

Cited by 33 publications

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“…In our study, fractional U Na V rates varied from Ͻ1% during control conditions to Ϸ4% during dual distal nephron blockade with AM plus BFTZ, suggesting predominant blockade of distal nephron transporters, epithelial sodium channels, and NCCs. If our dose of AM also inhibited the NHE isoform NHE3 in proximal tubules, we would have expected much greater increases in U Na V. Although proximal nephron effects cannot be ruled out, AM did not affect Li ϩ clearance in rats 35 and slightly increased fractional Li ϩ excretion in dogs. 36 However, the effect of AM to increase Li ϩ excretion may be because of inhibition of distal Li ϩ uptake in rats.…”

Section: Discussionmentioning

confidence: 78%

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Zhao

Navar

2008

Hypertension

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Abstract-Acute angiotensin II (Ang II) infusions into mice increase arterial pressure (AP) and elicit pressure natriuresis.We used this model of pressure natriuresis to delineate the distal nephron responses to AP-mediated increases in distal sodium delivery. In the first group, we measured changes in urinary sodium excretion (U Na V) in male C57/BL6 anesthetized mice (nϭ9) before and during acute Ang II infusions (5 ng/g of body weight per minute). Acute Ang II infusions increased AP (98Ϯ3 to 126Ϯ5 mm Hg; PϽ0.001), urine flow (2.7Ϯ0.5 to 6.0Ϯ0.8 L/min; PϽ0.01), and U Na V (0.6Ϯ0.2 to 1.3Ϯ0.2 Eq/min; PϽ0.05). There were significant relationships between U Na V and urine flow (yϭ0.207xϩ0.030; PϽ0.0001) and between U Na V and AP (yϭ0.027xϪ2.100). In a separate series, distal sodium delivery and fractional reabsorption of distal sodium delivery were determined in control (nϭ12) and Ang II-infused mice (nϭ8) by comparing U Na V before and after blockade of the 2 major distal nephron sodium transporters with amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight). A positive relationship was found between U Na V (yϭ0.015xϪ1.100; PϽ0.0001) or distal sodium delivery (yϭ0.027xϪ0.900; PϽ0.0001) and AP. An inverse relationship was found between fractional reabsorption of distal sodium delivery and AP (yϭϪ0.511xϩ128.300; PϽ0.01). These data indicate that Ang II-mediated pressure natriuresis involves an increase in distal sodium delivery combined with a reduced distal nephron fractional sodium reabsorption, suggesting that increased AP prevents the distal nephron transport mechanisms from accommodating the increased distal delivery. Key Words: Ang II Ⅲ arterial pressure Ⅲ renal sodium reabsorption Ⅲ distal nephron segments Ⅲ amiloride Ⅲ bendroflumethiazide Ⅲ fractional distal sodium reabsorption I t is well known that increases in arterial pressure (AP) lead to the increases in renal sodium excretion, a phenomenon commonly referred to as pressure natriuresis. [1][2][3][4][5][6][7][8] The changes in renal sodium excretion in response to changes in AP provide a link between the mechanisms regulating sodium excretion and those regulating AP. 1 Because glomerular filtration rate (GFR) and filtered sodium load are autoregulated over the same AP range, the mechanism of pressure natriuresis involves decreased tubular sodium reabsorption in response to increased AP; 6 however, the relative contributions of the various nephron segments responsible have not been fully defined. 5,9 -12 Acute angiotensin II (Ang II) infusions in mice and rats increase AP and elicit pressure natriuresis, suggesting that Ang II infusion is a useful model to delineate the relative contributions of the various nephron segments to increases in AP.The development of a mouse model with minimal surgical interventions to study pressure natriuresis would allow evaluation of the roles of specific tubular transport systems by using various gene targeted models. Although several studies have focused on the AP effects on proximal nephro...

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Section: Discussionmentioning

confidence: 78%

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Zhao

Navar

2008

Hypertension

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“…Endogenous lithium clearance is a well-established marker of proximal tubule sodium and water reabsorption and widely used in clinical investigations (14,16,17). Multiple animal studies document a reasonable estimate of proximal tubule reabsorption with lithium even though, in rats, there exists some evidence for distal reabsorption as well (18,20). Distal lithium reabsorption appears to predominate mainly when sodium intake is low; in our work here, diet sodium was set at 100 meq/day, an ample supply.…”

Section: Sodiummentioning

confidence: 92%

Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients

Worcester¹,

Coe²,

Evan³

et al. 2008

American Journal of Physiology-Renal Physiology

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. Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients. Am J Physiol Renal Physiol 295: F1286 -F1294, 2008. First published August 20, 2008 doi:10.1152/ajprenal.90404.2008.-A main mechanism of idiopathic hypercalciuria (IH) in calcium stoneforming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque. nephrolithiasis; tubule reabsorption; lithium clearance; hypercalciuria; proximal tubule IDIOPATHIC HYPERCALCIURIA (IH) is best described as a state of high urine calcium excretion commonly found in patients who form calcium renal stones and thought to play a causal role in such stones (22). Although gastrointestinal calcium absorption is above normal, offering an obvious mechanism for hypercalciuria, the kidney also participates. After eating common foods, patients with calcium stones and IH (IHSF) reduce their overall renal calcium reabsorption more than well-matched normal control subjects (23). This reduction permits high urine calcium losses despite unchanged serum calcium and calcium filtered load. Although serum parathyroid hormone decreases with meals, levels do so equally in IHSF patients and normal subjects, and therefore cannot be the main mechanism for the reduced tubule calcium reabsorption (23). Because the differential increase in urine calcium occurs without a corresponding difference of urine sodium between IHSF and normal, the cortical thick ascending limb of the loop of Henle was considered an attractive site of reduced calcium reabsorption (1) along with the distal convoluted tubule (8). Since filtered load of calcium did not differ between patients and normal subjects, hypercalciuria essentially arose from the change in tubule reabsorption.Which nephron sites participat...

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“…concentration ratios, single nephron glomerular filtration rate (SNGFR), tubular fluid-to-plasma ultrafiltrate (TF/UF) sodium and magnesium concentration ratios and fractional reabsorption (FR) of sodium and magnesium are expressed for the total number (given in parentheses) of tubules sampled. Sampson, 1992). In addition, values for UFMg and UFNa were within the normal range (see Table 2).…”

Section: Resultsmentioning

confidence: 61%

A new protocol for the measurement of picomole quantities of magnesium in rat renal tubular fluid

Kibble¹,

Audsley²,

Day³

et al. 1998

Experimental Physiology

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SUMMARYThe analysis of picomolar quantities of magnesium by electrothermal atomic absorption spectrophotometry (EAAS) was studied using a Perkin-Elmer-Zeeman 3030 spectrophotometer. The absorbance signal was not heavily dependent on the atomization temperature, but was greatly reduced when ashing temperatures in excess of 1200°C were applied. The magnesium signal was significantly depressed in the presence of excess chloride in the sample matrix. However, use of NH4NO3 as a matrix modifier was sufficient to overcome this artefact. The analytical sensitivity was 0 15 absorbance units pmol-' and the detection limit was 0.04 pmol. Using nanolitre constriction pipettes to dispense standards, the mean coefficient of variation was 5 %. Measurement of magnesium handling in the rat proximal convoluted tubule revealed a significant correlation between the tubular fluid-to-plasma ultrafiltrate (TF/UF) concentration ratio for magnesium and the tubular fluid-to-plasma (TF/P) concentration ratio for [3H]inulin (r2 = 0-56, n = 17). This indicated that magnesium is concentrated during its passage along the proximal tubule. In contrast, this was not the case for sodium (r2= 011, n = 16). Mean (TF/UF)Mg (1-16 + 007, n = 17) for random punctures was significantly greater than that for sodium ((TF/UF)Na = 1-02 + 0-02, n = 16). Despite concentration of magnesium in the lumen, significant net reabsorption of magnesium was observed along the length of the tubule (fractional reabsorption, FRMg = 19-4 + 3 0 %, n = 17). In conclusion, EAAS provides a highly sensitive, reproducible and technically simple method for measuring picomolar quantities of magnesium in renal tubular fluid.

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A micropuncture study of renal lithium reabsorption: effects of amiloride and furosemide

Cited by 33 publications

References 0 publications

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients

A new protocol for the measurement of picomole quantities of magnesium in rat renal tubular fluid

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