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D G Shirley

Publications and source records attributed to D G Shirley.

At least 37 records · Page 2Linked to original sources

Effect of vasopressin on renal lithium reabsorption: a micropuncture and microperfusion study.

Micropuncture techniques were used to investigate the nephron site(s) responsible for the vasopressin-induced reductions in lithium clearance and fractional lithium excretion (FELi) in anesthetized Brattleboro rats lacking endogenous vasopressin. In rats treated intravenously with the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP; 40 pg/min), FELi was significantly lower than in untreated animals (0.23 +/- 0.01 vs. 0.28 +/- 0.02, P < 0.05). Free-flow micropuncture showed that fractional lithium delivery (FDLi) to late proximal convolutions was identical in the two groups, whereas at the early distal tubule both FDLi (0.28 +/- 0.02 vs. 0.33 +/- 0.01, P < 0.05) and the tubular fluid-to-plasma lithium concentration ratio (1.18 +/- 0.04 vs. 1.36 +/- 0.06, P < 0.05) were lower in the DDAVP-treated group. No differences between the groups with respect to lithium handling beyond the early distal tubule were observed. In rats subjected to in vivo microperfusion of loops of Henle, intravenous infusion of DDAVP (40 pg/min) increased fractional lithium reabsorption in the loop from 0.56 +/- 0.03 to 0.66 +/- 0.04 (P < 0.05) and from 0.39 +/- 0.02 to 0.45 +/- 0.02 (P < 0.05) at perfusion rates of 10 and 15 nl/min, respectively. We conclude that DDAVP stimulates lithium reabsorption in the loop of Henle and suggest that this results from an increased transepithelial potential difference in the thick ascending limb.

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Role of volume status in vasopressin-induced natriuresis: studies in Brattleboro rats.

The influence of volume status on the effect of physiological doses of vasopressin on sodium excretion was assessed in anaesthetized Brattleboro rats. Following a 1 h control period, animals were divided into four groups. Group 1 (control) rats were kept in water balance throughout (by adjustment of the rate of i.v. glucose infusion) and received no vasopressin. In group 2 rats, vasopressin (20 microU/min) was infused i.v. for 2 h, then withdrawn during the following 2 h; the vasopressin-induced antidiuresis and subsequent return to water diuresis were matched by appropriate changes in the i.v. infusion, thus maintaining water balance. In this group, vasopressin had no effect on sodium excretion. Group 3 rats received the same dose of vasopressin, but the infusion rate of the glucose solution was not reduced; consequently these rats became water-loaded. In this group, sodium excretion increased significantly during vasopressin infusion, and rapidly returned to baseline values when the vasopressin was discontinued. Group 4 rats were treated in the same way as group 3 animals except that the vasopressin infusion was maintained (but without additional water loading) for a further 2 h; this did not prevent the fall in sodium excretion during the final 2 h of the experiment. We conclude that the natriuretic effect of physiological levels of vasopressin reported elsewhere may be dependent on an accompanying acute volume expansion during infusion of the hormone.

Animals↗

A micropuncture study of renal tubular lithium reabsorption in sodium-depleted rats.

1. The marked reduction in fractional lithium excretion (FELi) which accompanies chronic sodium depletion was investigated using free-flow micropuncture in anaesthetized rats which had been maintained in a sodium-depleted state for 8-10 days. 2. Compared with previous values in sodium-replete rats, sodium depletion was associated with small reductions in total and superficial nephron glomerular filtration rate and enhanced fractional reabsorption of water, sodium and lithium in the proximal convoluted tubule. 3. In untreated (sodium-depleted) rats, fractional deliveries of lithium (FDLi) to the late proximal convoluted tubule, early distal tubule and late distal tubule were 0.41 +/- 0.02, 0.20 +/- 0.01 and 0.18 +/- 0.02 (means +/- S.E.M.), respectively. Fractional lithium excretion (0.08 +/- 0.01) was significantly lower than late distal FDLi (P < 0.001). 4. Treatment with amiloride did not affect segmental lithium handling up to the late distal tubule. Frusemide had no effect on lithium reabsorption in the proximal convoluted tubule, but early distal FDLi (0.30 +/- 0.01) was raised compared with the untreated group (P < 0.001). Both diuretics eliminated the difference between late distal FDLi and FELi, respective values being 0.17 +/- 0.02 and 0.15 +/- 0.01 (amiloride-treated rats) and 0.31 +/- 0.02 and 0.34 +/- 0.02 (frusemide-treated rats). 5. These data indicate that part of the reduction in FELi in chronic sodium depletion is due to enhanced fractional fluid (and lithium) reabsorption in the proximal convoluted tubule. In addition, however, they provide direct evidence for amiloride-sensitive lithium reabsorption in the collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

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A micropuncture study of the renal response to haemorrhage in rats: assessment of the role of vasopressin.

The acute effects of haemorrhage (15 ml (kg body wt)-1) on renal function at whole-kidney and single-nephron levels were studied in Inactin-anaesthetized rats. In order to assess the role of vasopressin in mediating the haemodynamic effects, responses in untreated Long-Evans rats were compared with those in Brattleboro rats (which lack circulating vasopressin) and in Long-Evans rats treated with a V1 receptor antagonist. In time-control animals, there were no significant changes in mean arterial pressure (MAP), excretion rates, glomerular filtration rate (GFR), superficial-nephron GFR (SNGFR) or fluid reabsorption in the superficial proximal tubules during the course of the experiment. Following haemorrhage, the immediate reduction in MAP was followed in each group by partial recovery for 30 min; thereafter, MAP was stable. In untreated Long-Evans rats, haemorrhage was followed by a 26% reduction in GFR (P < 0.001, measured 60-150 min post-haemorrhage) and a larger reduction (45%, P < 0.001) in SNGFR, so that the SNGFR/GFR ratio fell significantly ((27.9 +/- 1.9) x 10(-6), control period; (20.2 +/- 2.2) x 10(-6) post-haemorrhage, P < 0.01). Slightly greater reductions in GFR and SNGFR were seen in Brattleboro rats and V1 antagonist-treated Long-Evans rats, which corresponded to slightly greater haemorrhage-induced reductions in blood pressure in these groups; the falls in the SNGFR/GFR ratio were similar to that in untreated Long-Evans rats. In all three groups of bled rats, fractional reabsorption by the proximal convoluted tubule increased slightly 30-60 min after haemorrhage, but during the subsequent period (60-150 min) returned to values indistinguishable from those during the control period. The results suggest that the renal haemodynamic changes that follow moderate haemorrhage include a preferential reduction in the GFR of superficial nephrons. Vasopressin appears to play no role in this response. Increases in fractional reabsorption in the proximal tubules are seen only during the immediate post-haemorrhage period.

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The natriuretic effect of lithium in man: is the proximal tubule involved?

The possible role of the proximal tubule in the natriuresis which follows the administration of small doses of lithium, as used in lithium clearance studies, was investigated in 12 healthy males on a fixed sodium intake. Subjects were given placebo tablets, or 100 mg or 600 mg of lithium carbonate; renal function was assessed 3-6 h later. The 600-mg dose of lithium carbonate caused a 50-60% increase in sodium excretion, whereas the 100-mg dose was without effect. Creatinine clearance, used as an index of glomerular filtration rate, was unaffected by either dose. Three indices of end-proximal fluid delivery were used simultaneously: urine flow rate during suppression of vasopressin secretion (Vmax), phosphate clearance and lithium clearance (the latter only on the days on which lithium was administered). No effect of either dose of lithium on Vmax or phosphate clearance was evident; nor was there a difference between values for lithium clearance following the two doses. We conclude that administration of the standard 600-mg test dose of lithium carbonate does not affect proximal tubular function.

Adult↗

The effect of chronic sodium depletion on renal function in conscious rats.

In order to investigate the effect of chronic sodium depletion on renal proximal tubular reabsorption, studies were performed in conscious, unrestrained Brattleboro rats. Since these animals lack circulating vasopressin, fractional water reabsorption in the distal nephron can be assumed to be constant and changes in urine flow rate should therefore reflect changes in end-proximal fluid delivery. Sodium depletion was induced by placing rats on a low-sodium diet (4 mmol Na (kg dry wt)-1) and administering frusemide (40 mg (kg body wt)-1) by gavage on the first 2 days. Extracellular volume, measured after 7-9 days, was reduced by 19% (P < 0.02) as compared with that of rats maintained on a control diet. Urine flow rate, measured during days 4-7 of the low-sodium diet, was significantly lower than that of control rats (142 +/- 8 vs. 168 +/- 5 ml day-1, P < 0.01). Since renal papillary interstitial fluid osmolality was found to be reduced in the sodium-depleted rats (693 +/- 38 vs. 812 +/- 36 mosmol (kg H2O)-1, P < 0.05), it is unlikely that water reabsorption from sites beyond the proximal tubule had increased. The observed reduction in urine flow rate therefore strongly suggests a reduction in end-proximal fluid delivery. In the second part of the study, a single group of Brattleboro rats was used, in which osmotic minipumps were implanted in the peritoneal cavity for continuous infusion of [14C]inulin. After recovery from the operation, the rats were maintained on a control diet for 6 days (pre-control period), then subjected to sodium depletion (low-sodium diet for 6 days, frusemide administration on the first 2 days), and finally returned to the control diet for 6 days, with access to 0.46 M NaCl solution on the first 2 days, in order to restore sodium balance (post-control period). On the final 2 days of each phase, urine flow rate and [14C]inulin clearance (= glomerular filtration rate, GFR) were measured. Urine flow rates during the pre-control, sodium depletion and post-control periods were 169 +/- 7, 132 +/- 8 (P < 0.001) and 176 +/- 8 microliters min-1, respectively; corresponding values for fractional water excretion were 7.0 +/- 0.3, 6.0 +/- 0.5 (P < 0.01) and 7.4 +/- 0.4%. Only a small reduction GFR, of borderline statistical significance, was observed during sodium depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Lithium reabsorption in perfused loops of Henle: effects of perfusion rate and bumetanide.

The contribution of the loop segments to lithium reabsorption in sodium-replete, anesthetized Sprague-Dawley rats was examined by perfusing superficial loops of Henle between late proximal convolutions and early distal tubules. Preliminary experiments in which lithium was initially present only inside or outside the perfused loop confirmed substantial permeability of one or more of the loop segments to lithium. In subsequent experiments, in which lithium was infused intravenously and included in the perfusate so that the perfusate-to-plasma lithium concentration ratio was close to that found in late proximal tubules during lithium clearance studies, lithium reabsorption was inversely related to the perfusion rate: values for fractional lithium reabsorption (FRLi) at perfusion rates of 10, 20, and 30 nl/min were 58 +/- 3, 17 +/- 2, and 2 +/- 2%, respectively. Bumetanide (10(-6) M) markedly inhibited FRLi but also reduced water reabsorption, suggesting an effect on the pars recta at this dose; 10(-7) M bumetanide, which was without effect on water reabsorption, had only a small effect on FRLi at a perfusion rate of 10 nl/min but reduced FRLi by approximately 70% at 20 nl/min. We argue that the remarkable flow dependency of lithium reabsorption, together with its bumetanide sensitivity, provides evidence for significant voltage-driven lithium reabsorption in the thick ascending limb of Henle.

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Simulation of lithium transport along the thin segments of Henle's loop.

Although the renal clearance of lithium is widely used as an index of sodium and water delivery to the end of the proximal tubule, micropuncture studies of superficial nephrons suggest that lithium may be reabsorbed additionally in the loop of Henle. In order to examine the possibility of lithium transport in the thin loop segments of deep nephrons, we conducted a computer simulation study using a modification of the mathematical model reported previously. The data for the model were obtained from measurements of osmolality and electrolyte concentrations in systemic plasma and renal papillary interstitial fluid of control and furosemide-treated rats. Papillary interstitium/plasma Li+ concentration ratios were 3.23 and 1.48 in the control and the furosemide group, respectively. Assuming that solute concentration in the renal medulla increases as an exponential function, and applying phenomenological coefficients obtained from hamsters, the transport profiles of Li+ along the thin loop segments were calculated to be very similar to those of Na+. In the control group, about 82% of delivered Li+ was reabsorbed along the entire thin loop segments, with all segments contributing equally. This value may represent the highest possible capacity of the thin loop segments. In the furosemide group, Li+ reabsorption in the thin loop was reduced to 31% of delivered Li+. From these analyses, we conclude that an appreciable amount of lithium may be reabsorbed in the thin loop segments of long-looped nephrons by passive mechanisms. Furosemide inhibits Li+ reabsorption by dissipating the osmotic concentration gradient in the renal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

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

The validity of the lithium clearance technique as a measure of end-proximal fluid delivery was assessed using micropuncture in sodium-replete, Inactin-anesthetized Sprague-Dawley rats. Three groups of animals were used: controls, amiloride treated, and furosemide treated. Diuretic-induced salt and water losses were replaced. Fractional lithium excretion (FELi) was 0.23 +/- 0.01, 0.24 +/- 0.02, and 0.40 +/- 0.03 in the control, amiloride, and furosemide groups, respectively. In each group, the tubular fluid-to-plasma lithium concentration ratio at the end of the proximal convoluted tubule (PCT) was significantly greater than unity (control, 1.16 +/- 0.03; amiloride, 1.16 +/- 0.02; furosemide, 1.17 +/- 0.02). In the control group, fractional lithium delivery (FDLi) at the late PCT was 0.50 +/- 0.02, while FDLi at the early distal tubule was 0.25 +/- 0.01; the latter did not differ significantly from FDLi at the late distal tubule or from FELi. Values in amiloride-treated rats were almost identical. Furosemide had no effect on FDLi at the late PCT, but raised that at the early distal tubule to 0.37 +/- 0.03. We conclude that 1) lithium reabsorption in the PCT lags slightly behind that of water, 2) substantial furosemide-sensitive lithium reabsorption occurs beyond the PCT, and 3) no significant lithium reabsorption occurs in nephron segments beyond the loop. These findings call into question the use of lithium clearance as a quantitative measure of end-proximal fluid delivery in sodium-replete animals.

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Acute and chronic changes in renal function following unilateral nephrectomy.

Free-flow micropuncture was used to assess proximal and distal tubular function in rats immediately (2 to 5 hours), five days and 30 days after uninephrectomy (UN); results were compared with those in sham-operated littermates. Excretion rates of water, sodium and potassium were approximately doubled in the remaining kidney of UN rats. Two to five hours after UN there were small increases in glomerular filtration rate (GFR) and single nephron GFR which at this stage were not accompanied by an increase in absolute proximal reabsorption; that is, fractional proximal reabsorption fell. After five days, GFR and single nephron GFR had increased further; at this stage absolute proximal reabsorption was also significantly elevated. After 30 days, kidney weight, GFR, single nephron GFR and absolute proximal reabsorption had all increased by approximately 40%, and glomerulotubular balance in the proximal tubule had been fully restored. Data derived from distal tubular collections indicated that at every stage after UN: (a) fluid delivery to both early and late distal puncture sites was increased; (b) in contrast, there was no increase in sodium delivery to the late distal tubule, suggesting that the natriuresis resulted from reduced sodium reabsorption beyond the distal tubule and/or increased delivery of sodium from deep nephrons; and (c) there was a marked increase in potassium secretion into the accessible portion of the distal tubule which was more than adequate to explain the observed kaliuresis.

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How important are suppression of aldosterone and stimulation of atrial natriuretic peptide secretion in the natriuretic response to an acute sodium load in man?

1. Aldosterone is suppressed by sodium loading. We studied the contribution of this decrease in plasma aldosterone to the natriuresis after acute sodium loading in healthy volunteers. 2. Two litres of saline [0.9% (w/v) NaCl] were infused during the second hour of a 6 h infusion of aldosterone (3 pmol min-1 kg-1) or placebo in eight healthy young men. On the placebo day, plasma aldosterone decreased by 30 min after the start of saline infusion and remained suppressed. During aldosterone infusion, plasma aldosterone was maintained at around 400 pmol/l. 3. Urinary sodium excretion, lithium clearance and plasma atrial natriuretic peptide increased and plasma renin activity decreased after saline infusion, whether or not aldosterone was infused. However, from 60 to 240 min after saline infusion, natriuresis was significantly less during aldosterone infusion than on the placebo day. In addition, saline loading led to a progressive increase in the ratio of sodium clearance to lithium clearance, used as an index of the fractional distal tubular rejection of sodium, and in the ratio of urinary sodium to potassium. These increases were prevented by the infusion of aldosterone. 4. This study suggests that there are differences in the mechanisms determining the early and the later responses to an acute sodium load. Suppression of aldosterone may explain much of the later increase in natriuresis after saline infusion. In addition, the results are consistent with a role for atrial natriuretic peptide in the immediate increase in sodium excretion after saline loading.

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Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man.

1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours. 2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates. 3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P less than 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed. 4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P less than 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P less than 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period. 5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P less than 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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The renal vascular response to mild and severe haemorrhage in the anaesthetized rat.

1. In order to document the characteristics of the renal vascular response to blood losses of varying severity, Inactin-anaesthetized rats were subjected to a haemorrhage of 5, 10, 15 or 20 ml (kg body weight)-1, while a fifth group (control rats) remained unbled. Radioactive microspheres (diameter 10 microns) were used to determine cardiac output, total renal blood flow and the distribution of blood flow within the kidneys; measurements were made before and 5-120 min after haemorrhage. 2. In control animals none of the variables studied changed significantly during the experimental period. 3. Immediately after haemorrhage there were reductions in arterial pressure and cardiac output which were roughly proportional to the severity of haemorrhage. Arterial pressure recovered to some extent during the next 30 min, then stabilized; cardiac output recovered only slightly. 4. Total renal blood flow fell to an extent dependent on the degree of haemorrhage, with no evidence of subsequent recovery. The approximate reductions in renal blood flow were 2% (n.s.), 15%, 30% and 50% after bleeds of 5, 10, 15 and 20 ml kg-1, respectively. Renal vascular resistance increased consistently only in the groups bled 15 and 20 ml kg-1. When renal blood flow was expressed as a fraction of cardiac output, it increased during the period immediately after haemorrhage, indicating some degree of 'protection' of the renal circulation in the face of hypotension. 5. Measurements of intrarenal blood flow indicated a significantly reduced flow to the superficial cortex after every degree of haemorrhage. Inner cortical flow was less affected and fell significantly only in the groups bled 15 and 20 ml kg-1; blood flow to the mid-cortex was intermediate.

Anesthesia↗

Effect of frusemide on lithium clearance and proximal tubular reabsorption in anaesthetized rats.

1. In order to investigate the lithiuretic effect of frusemide, simultaneous measurements of fractional lithium excretion (FELi) and fractional fluid delivery to the end of the proximal convoluted tubules were made in Inactin-anaesthetized rats, first during a control period, then during intravenous infusion of frusemide at either 0.8 or 8.0 mg kg-1 h-1. Fluid balance was maintained by infusion of NaCl-KCl solution adjusted to match urinary excretion rates; measurements were made after urine flow had stabilized. 2. In time-control animals, which did not receive frusemide, no significant changes were observed in either FELi or fractional fluid delivery to the end of the proximal convoluted tubules (determined as the plasma/tubular fluid inulin concentration ratio, P/TFIn). 3. In animals given the high dose of frusemide, FELi increased from 0.22 +/- 0.02 (mean +/- S.E.M.) during the control period to 0.45 +/- 0.03 during frusemide infusion (P less than 0.001); this was accompanied by a modest increase in P/TFIn, from 0.43 +/- 0.02 to 0.51 +/- 0.02 (P less than 0.01). 4. In animals given the lower dose of frusemide, FELi increased from 0.21 +/- 0.01 to 0.37 +/- 0.01 (P less than 0.001). In this group, however, there was no discernible change in P/TFIn (0.43 +/- 0.02 vs. 0.44 +/- 0.01, not significant). 5. These results suggest that under control conditions a significant component of lithium reabsorption may occur beyond the proximal tubule, most likely in the loop of Henle.

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Renal function in normal and potassium-depleted rats before and after preparation for micropuncture experimentation.

Renal function was examined in unrestrained conscious rats maintained on either a control diet or a low-potassium diet, then re-examined in the same animals after thiobutabarbital (Inactin) anaesthesia and preparation for micropuncture studies. In conscious rats, insulin clearance (CIn) was not significantly different in the two groups (control 1012 +/- 43, low-K 904 +/- 58 microliters/min per 100g body wt; mean +/- SE), but lithium clearance (CLi; used as an estimate of end-proximal fluid delivery) and fractional lithium excretion (FELi) were substantially reduced in the low-K group (CLi: 246 +/- 11 vs 126 +/- 8 microliters/min per 100g body wt, P less than 0.001; FELi: 0.245 +/- 0.009 vs 0.143 +/- 0.008, P less than 0.001). Following anaesthesia and preparation for micropuncture, there were significant reductions in urine flow rate and sodium excretion in the control group, but not in the low-K rats. Potassium excretion increased in both groups, but values in the potassium-depleted animals remained extremely low. In neither group of rats was preparation for micropuncture associated with significant changes in CIn, CLi or FELi. Thus, differences in tubular function between control and potassium-depleted rats were still apparent. The results suggest that preparation for micropuncture disturbs the function of the distal nephron, but that rates of glomerular filtration and proximal tubular reabsorption remain similar to values in conscious animals.

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Analysis of the relation between lithium clearance and sodium clearance in rats.

In rats on a normal or high sodium intake, lithium clearance (CLi) is thought to approximate fluid delivery to the end of the proximal tubule (Vprox), whereas in rats on a very low sodium intake CLi is lower than Vprox owing to significant reabsorption of lithium in the distal nephron. This paper examines the relation between CLi and sodium clearance (CNa) in animals adapted to a range of dietary sodium contents (5-300 mmol/kg). Measurements were performed in conscious, unoperated rats with hereditary diabetes insipidus, in which changes in urine flow rate (V) can be used as an index of changes in Vprox; stimulation of distal lithium reabsorption was identified by comparing changes in CLi with the corresponding changes in V. CLi exhibited a curved, positive relation with CNa, with considerable scatter and a sharp decrease of CLi at low values of CNa. Further analysis indicated that this relationship consisted of three elements: (i) an almost unaltered Vprox in response to variations in dietary sodium: taken alone, this would result in a horizontal regression of CLi on CNa. (ii) Distal reabsorption of lithium in rats on very low sodium intakes, bending the curve towards low CLi values at low values of CNa. (iii) Intra-individual variations in Vprox, causing covariation of CLi and CNa; the slopes of the regression lines linking the two depended on the level of sodium intake, but all the regression lines intercepted the CLi axis at a similar (low) value of CLi, making a major contribution to the curved shape of the relationship. It is concluded that observations of greatly reduced values of CLi at low values of CNa cannot be taken as unequivocal evidence, per se, of distal reabsorption of lithium. Nor should measured values of CLi be corrected for differences in CNa.

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The influence of posture on renal tubular function in man.

The acute effects of changes in posture on renal function were investigated in healthy volunteers. Proximal tubular function was assessed using two methods simultaneously: lithium clearance and urine flow rate during maximal water diuresis. Changing from the standing to the supine posture was associated with significant increases in urine flow rate and in the clearances of sodium, potassium, creatinine and lithium (p less than 0.01 in each case). Increases in fractional water excretion and fractional lithium excretion (using creatinine clearance as an estimate of glomerular filtration rate) were also observed (p less than 0.01). The increases in lithium clearance and urine flow rate, both absolute and fractional, were significantly correlated. These findings suggest that the acute increase in sodium excretion following assumption of the supine posture results largely from an increase in end-proximal fluid delivery, due partly to an increase in glomerular filtration and partly to a decrease in fractional reabsorption in the proximal tubule. The results also provide circumstantial support for the use of lithium clearance as a marker of end-proximal delivery in man.

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