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Biomedical subjects

W H Boer

Publications and source records attributed to W H Boer.

At least 37 records · Page 2Linked to original sources
PubMed1993

Prostaglandin synthesis inhibition stimulates lithium reabsorption in Henle's loop in rats.

The effect of prostaglandin (PG) synthesis inhibition on tubular lithium (Li) handling in the rat was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules. Animals received no treatment (N = 7), meclofenamate (MECLO; 5 mg/kg i.p. and 5 mg/kg i.v.; N = 7) or indomethacin (INDO, 1 mg/kg i.v.; N = 6). Whole kidney fractional Li excretion fell from 26.2 +/- 1.5% in control rats to 12.8 +/- 1.3% and 14.6 +/- 1.3% in MECLO and INDO treated rats. Fractional delivery of Li to the LPT was not affected by PG synthesis inhibition. All of the rise in tubular Li reabsorption took place between the LPT and EDT; at the EDT fractional Li delivery fell from 32.3 +/- 2.0% in the control group to 19.1 +/- 1.6% and 20.0 +/- 1.4% in the rats given MECLO or INDO. Water reabsorption between the LPT and EDT also increased. The tubular fluid/plasma Li concentration ratio ([T/P]Li) at the LPT was approximately 1.15 in all groups of rats. At the EDT, this ratio was approximately 1.06 in control rats, but only approximately 0.82 (P < 0.01) in rats subjected to PG synthesis inhibition. The finding that the [T/P]Li fell from values exceeding unity at the LPT to values below unity at the EDT during PG synthesis inhibition indicates that reabsorption of Li between these sites was stimulated to a greater extent than that of water. This dissociation strongly suggests that at least part of the increased Li reabsorption between the LPT and EDT took place in the water-impermeable thick ascending limb.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Effects of furosemide or acetazolamide infusion on renal handling of lithium: a micropuncture study in rats.

Renal lithium (Li) handling was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules in control rats and rats infused with furosemide (FUR) or acetazolamide (ACTZ). In control rats, the tubular fluid-to-plasma Li concentration ratio [(T/P)Li] at the LPT exceeded unity (1.05 +/- 0.02, P < 0.05). Some 25% of the filtered load (FL) of Li and water was reabsorbed in proportion between the LPT and the EDT, and consequently the (T/P)Li at the EDT (1.03 +/- 0.03) did not change. FUR inhibited Li reabsorption in the proximal convoluted tubules (PCT), by approximately 7% of the FL. Reabsorption of Li and water in the loop segment was also inhibited, virtually in proportion, by approximately 10% of the FL. These data suggest that FUR-sensitive Li reabsorption in the loop mainly takes place in the pars recta. However, a small increase in the (T/P)Li at the EDT (to 1.10 +/- 0.01) suggested inhibition of some Li transport (approximately 2% of the filtered load of Li) without water, most likely in the thick ascending limb (TAL). In the PCT, ACTZ reduced Li reabsorption by approximately 16% of its FL. Although it is likely that ACTZ also inhibited the pars recta, net Li reabsorption in the loop was not reduced. This suggests that TAL Li reabsorption can compensate for increased delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Indomethacin- and desamino-8-D-arginine vasopressin-induced lithium reabsorption is not amiloride sensitive in humans.

This study was undertaken to analyze whether the mechanism of decreased fractional lithium excretion (FELi) induced in humans by the prostaglandin synthesis inhibitor indomethacin and the vasopressin analog desamino-8-D-arginine vasopressin (d-DAVP) is amiloride inhibitable. Eight sodium-restricted (10 mmol/day) healthy volunteers underwent clearance studies to evaluate the effects of indomethacin (50 mg tid for 6 days), amiloride (10 mg twice before the clearance study) and d-DAVP (4 micrograms, i.v.), and combinations of these drugs. Despite the sodium restriction, amiloride had no effect on FELi, although the dosage was sufficient to cause a 6-fold increase in sodium excretion, and potassium retention. Compared to a base-line value of 27.9 +/- 2.1%, FELi fell to 20.7 +/- 2.1% after indomethacin (P < .01) and to 22.4 +/- 1.5% after d-DAVP (P < .01). When d-DAVP was administered during indomethacin, the FELi fell to 18.0 +/- 1.4%. Compared to indomethacin alone, this represented no significant further change. Amiloride did not prevent the fall in FELi caused by indomethacin or d-DAVP or both. These data indicate that in humans, 1) sodium restriction does not cause amiloride-sensitive lithium reabsorption, and 2) the lithium reabsorption caused by d-DAVP and indomethacin is not amiloride sensitive.

Absorption↗
PubMed1992

Amiloride-sensitive lithium reabsorption in rats: a micropuncture study.

It has been suggested that in sodium-restricted rats lithium is being reabsorbed in the collecting tubule, and that such reabsorption can be prevented by amiloride. We studied these options in rats by means of cortical micropuncture. Indeed, an important fraction of the filtered lithium (10.5%) was reabsorbed beyond the early distal tubule in sodium-restricted rats. Amiloride infusion abolished this reabsorption. The dosage used did not affect the reabsorption of water, sodium and lithium in the proximal tubule, and also did not change the reabsorption of water and sodium in the loop segment. However, the reabsorption of lithium in this segment tended to be higher during amiloride (P = .06), and the delivery of lithium to the early distal puncture site was significantly less (26.1 +/- 1.2%) than in the control rats (31.4 +/- 1.8%, P < .05). The reason for this apparent increase in lithium reabsorption in the loop segment is not clear. Interestingly, amiloride increased urine flow and decreased urine osmolality. The mechanism underlying this effect needs further exploration. We conclude that in sodium-restricted rats lithium reabsorption beyond the early distal tubule level occurs. Lithium clearance data therefore underestimate end-proximal delivery under these conditions. Lithium reabsorption beyond the early distal tubule can be prevented by amiloride treatment. However, because amiloride may stimulate lithium reabsorption further upstream, lithium clearance data obtained during amiloride infusion may still underestimate end-proximal delivery of water and sodium.

Absorption↗
PubMed1992

Impaired diluting segment chloride reabsorption in patients with cystic fibrosis.

Clearance studies were performed in 12 patients with cystic fibrosis (CF) during maximum water diuresis. The fractional diluting segment reabsorption was calculated from chloride clearance (CCl) and maximum free water clearance (CH2O) as 'CH2O/CCl+CH2O'. Fractional delivery to the diluting segment and from the proximal tubules was estimated by maximum urine flow during water diuresis (Vmax/GFR) and lithium clearance (CLi/GFR), respectively. The data were compared with results obtained in young healthy subjects. To estimate free water generation beyond the medullary diluting segment, CH2O/GFR was also measured during acute furosemide administration in 5 patients. Values for the term CH2O/CCl+CH2O were significantly lower in patients with CF (79.1 +/- 5.1%) as compared with healthy controls (89.4 +/- 4.4%). This was also true for the terms Vmax/GFR (CF: 9.5 +/- 1.6%; control subjects: 13.8 +/- 2.5%) and CLi/GFR (CF: 22.2 +/- 4.1%; control subjects: 30.7 +/- 5.1%). Compared to data derived from the literature, the solute-free water generation during administration of furosemide (CH2O/GFR) was significantly reduced in patients with CF (6.8 +/- 1.5%) as compared with healthy subjects (13.3 +/- 6.1%). We conclude that reabsorption in the diluting segment is impaired in patients with CF, perhaps at a site beyond the thick ascending limb of Henle's loop. Enhanced proximal reabsorption, suggested by reductions in Vmax/GFR and CLi/GFR, appears to be a compensatory phenomenon to maintain sodium and chloride balance.

Absorption↗
PubMed1992

Comparative study of the effects of furosemide, ethacrynic acid and bumetanide on the lithium clearance and diluting segment reabsorption in humans.

The effect of intravenous administration of the loop diuretics bumetanide, furosemide and ethacrynic acid on lithium (Li) clearance (CLi) and diluting segment reabsorption was studied in seven healthy water-loaded men. According to the increments in minimal urine osmolality (Uosm), ethacrynic acid (which increased Uosm from 59 +/- 4 to 233 +/- 3 mOsmol/kg) had the strongest inhibiting effect on diluting segment reabsorption, whereas that of furosemide and especially bumetanide was significantly less pronounced (rise in Uosm from 56 +/- 3 to 222 +/- 4 and 56 +/- 4 to 192 +/- 2 mOsmol/kg, respectively). In contrast, ethacrynic acid induced a significantly smaller rise in CLi (approximately 14% of the filtered load of Li) than furosemide and bumetanide, which increased Li excretion by approximately 23% and approximately 24% of its filtered load. The observation that the loop diuretic with the most pronounced inhibiting effect in the diluting segment had the smallest effect on CLi makes is unlikely that the increase in CLi induced by loop diuretics is predominantly effected in Henle's loop.

Adult↗
PubMed1990

Does lithium clearance reflect distal delivery in humans? Analysis with furosemide infusion.

Fractional excretion of lithium (FELi+) has been proposed as an index of fluid delivery to the distal nephron. The increase in FELi+ after the "loop diuretic" furosemide indicates that this postulate may not be valid unless furosemide acts in the proximal tubules. We studied the effect of furosemide (40 mg iv as bolus, followed by 20 mg/h infusion for 90 min) in eight healthy male subjects during maximal water diuresis. Special care was taken to exactly replace urinary losses. Furosemide greatly increased fractional excretion of sodium, from 1.3 +/- 0.4 to 27.8 +/- 3.9%, and water, from 14.2 +/- 1.7 to 38.2 +/- 3.7% (P less than 0.01). There was a disproportionately large increase in FELi+ from 30.3 +/- 3.0 to 53.7 +/- 2.9% (P less than 0.01), whereas fractional excretion of some other alleged proximal markers increased to a lesser extent. Lysine vasopressin, infused at the end of the experiment (n = 7), caused only a small increase in urine osmolality from 225 +/- 17 to 241 +/- 17 mosmol/kg (P less than 0.01), indicating that medullary hyperosmolality had been largely abolished. The most likely explanation of these results is that furosemide has a moderate action in the proximal tubules, and at the same time inhibits preexistent lithium absorption in Henle's loop. In addition, the large difference between FELi+ and maximal urine flow remaining after furosemide suggests that, despite the decreased medullary osmotic gradient, water backdiffusion is unaltered by furosemide or that lithium concentration in the proximal tubule is changed by furosemide.

Diuresis↗
PubMed1990

Renal hemodynamic and tubular response to furosemide in man during normal and restricted sodium intake.

To investigate the factors determining the natriuretic response to furosemide (F) during Na restriction, we performed clearance studies in 7 healthy humans on a daily Na intake of 200 and 20 mmol. The maximum urine flow during water loading (Vmax) and simultaneous F administration was used as index of tubular fluid output from the proximal tubules. The F-induced natriuresis was only moderately reduced during Na restriction (Na excretion on low vs. normal Na intake: 4.28 +/- 0.25 vs. 4.94 +/- 0.25 mmol/min; p less than 0.05). The diminished natriuresis was mainly due to a significant fall in Na delivery to Henle's loop of 0.51 +/- 0.10 mmol/min which was either caused by a decrease in filtered Na load or a rise in fractional proximal reabsorption. Fractional distal Na reabsorption was less suppressible by F during Na restriction, but this contributed relatively little (0.15 +/- 0.11 mmol/min) to the total reduction in Na excretion (0.66 +/- 0.10 mmol/min). The F-induced increases in uric acid, phosphate, and bicarbonate excretion suggest an additional proximal site of action of F. This was confirmed by a rise in lithium clearance (CLi), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in CLi to values markedly exceeding Vmax suggest that CLi overestimates tubular fluid delivery to Henle's loop during F administration.

Adult↗
PubMed1989

Beta-blockade disappearance rate predicts beta-adrenergic hypersensitivity.

We determined whether the beta-blockade disappearance rate would determine the degree of subsequent transient beta-adrenoceptor hyperresponsiveness after abrupt withdrawal of a beta-adrenoceptor drug. In a single-blind randomized study, 10 healthy men took a placebo for 1 week and then took nadolol one time a day (t1/2, 18 to 24 hours) or propranolol three times a day (t1/2, 4 to 6 hours) in doses that were increased weekly for 4 weeks to reach 240 mg per day. beta-Receptor responsiveness was assessed before and repeatedly after abrupt drug withdrawal by infusion of isoproterenol and epinephrine and by ergometer exercise. In the 13 days after drug discontinuation, peak beta-receptor sensitivity correlated (p less than 0.05) with the disappearance rate of beta-blockade as assessed by heart rate responses to isoproterenol (r = 0.68) and to submaximal exercise (r = 0.62) and by diastolic blood pressure responses to isoproterenol (r = 0.86) and epinephrine (r = 0.86). Plasma catecholamine levels and renin activity showed no overshoot. beta-Blockers with long plasma t1/2 values may prevent beta-blocker withdrawal syndromes by means of "self-tapering."

Adult↗
PubMed1989

Small intra- and large inter-individual variability in lithium clearance in humans.

We report the inter- and intra-individual variability in fractional lithium clearance (CLi), an alleged quantitative index of Na and water delivery from the proximal tubules, in humans (N = 91). The inter-individual variability was large, the variation coefficients at various Na excretion rates ranging between 11% and 19%. The intra-individual variability was small, the relative intra-individual standard deviation for duplicate measurements (N = 33) being 5%. These observations suggest large inter-individual differences in proximal tubular Na reabsorption. To confirm this, we also studied the inter- and intra-individual variability in the maximum urine flow during water diuresis (Vmax), an index of Na delivery to the diluting segment. They were found to be almost identical to the inter- and intra-individual variability in CLi, and fractional CLi and Vmax correlated strongly (r = 0.83, P less than 0.001). In addition, the inter-individual variability in the fractional clearance of uric acid (CUA), a directional marker of Na reabsorption in the proximal tubules, was large, but the intra-individual variability small. The correlation between fractional CUA and CLi, however, was relatively weak (r = 0.40, P less than 0.01). Although our results do not prove the exact, quantitative validity of the lithium clearance concept, we conclude that the variability in CLi reflects large inter-individual differences in Na handling in the proximal segments of the nephron. Our observations also have implications for the use of the lithium clearance method. The large inter-individual variability in CLi makes the method less suitable to detect subtle differences in CLi in small, unpaired groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1989

Evaluation of lithium clearance as a marker of proximal tubule sodium handling.

Estimations of proximal tubule sodium reabsorption with the FELi method come closer to direct measurements than any other indirect method. There is little doubt that most lithium reabsorption takes place in the proximal tubules, very likely in proportion to the reabsorption of sodium and water. It is also likely that changes in proximal tubule sodium reabsorption due to changes in volume status are paralleled by changes in proximal tubule lithium reabsorption, at least in the superficial nephrons. Nonetheless, changes in FELi probably do not purely reflect changes in proximal reabsorption, since lithium is also handled beyond the proximal tubules. Acknowledged problems are lithium reabsorption in Henle's loop and in the late distal and collecting tubules. The latter occurs in the rat and the dog, but not or much less in men. Sodium restriction enhances this lithium transport considerably. It is as yet uncertain whether other conditions, such as increased vasopressin activity or lowering of renal perfusion pressure, also influence this transport. Amiloride appears to prevent this reabsorption of lithium. Therefore, this drug can be used in lithium clearance studies whenever unwanted "distal" lithium reabsorption is expected. Lithium reabsorption in Henle's loop forms a greater problem as it cannot be prevented by any drug without influencing proximal tubule reabsorption. It is estimated that about 7% of the filtered lithium (one-tenth of total lithium reabsorption) is normally taken up here, preferentially in deep nephrons. In view of studies with furosemide, this reabsorption probably varies with sodium intake, but the proportion of this variation to that of proximal tubule lithium reabsorption is obscure. This remains an uncertain factor in any circumstance where the lithium clearance method is used. In some conditions the change in FELi may be so large relative to the expected changes in proximal reabsorption, that use of FELi as marker of end-proximal solute delivery seems unjustified. Disproportionately large suppression is likely during mineralo-corticoid-induced volume expansion, and stimulation during prostaglandin synthesis inhibition and vasopressin. Based on observations in these conditions the potential range of lithium reabsorption in the loop of Henle would be 0 to 15% of filtered load. In this review attention was paid mainly to the validity of lithium clearance as a pure "proximal marker". Many of our interpretations suffer from incomplete certainty with respect to the renal effects of tested maneuvers, a problem which is acknowledged.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man.

1. The acute effects of chlorothiazide and bendroflumethiazide on renal Li+ clearance (CLi) were studied in Na+-restricted healthy humans during maximum water diuresis. 2. Chlorothiazide, which has marked carbonic anhydrase inhibiting activity, increased CLi by about 25%. The concomitant rise in uric acid clearance, maximum urine flow and bicarbonate excretion suggests that this drug suppressed proximal reabsorption through carbonic anhydrase inhibition, which would also explain the observed fall in glomerular filtration rate (increased glomerulotubular feedback activity). 3. Bendroflumethiazide, which lacks carbonic anhydrase inhibiting activity, did not affect CLi or any of the other above-mentioned variables. 4. It is concluded from the lack of an effect of bendroflumethiazide on CLi that Li+ is not reabsorbed in thiazide-sensitive segments of the human distal nephron. The rise in CLi after chlorothiazide is most likely due to suppressed Li+ reabsorption in the proximal tubules resulting from carbonic anhydrase inhibition. 5. The results of this study are compatible with the concept that CLi is an index of Na+ and water delivery from the proximal tubules in humans.

Bendroflumethiazide↗
PubMed1989

Urinary angiotensin excretion during sodium restriction and diuretics.

The urinary excretion rate and plasma concentration of angiotensin I (UAI, PAI) and angiotensin II (UAII, PAII), and plasma renin activity (PRA) were measured in seven healthy volunteers in the supine and upright position both on free and restricted sodium intakes. The same variables were measured before and after intravenous injection of furosemide, as well as before and during intravenous infusion of chlorothiazide. Assumption of the upright posture as well as sodium restriction increased PAI, PAII, and PRA, but UAI and UAII excretion were not altered by these manoeuvres. Furosemide injection resulted in increases of all variables, albeit that PAI and PAII were elevated to a lesser extent then PRA. Chlorothiazide infusion caused a reduction in PAI, PAII, and PRA, whereas UAI and UAII excretion increased modestly. The discrepancies between changes in plasma and urinary AI and AII may indicate that urinary angiotensin excretion provides information which is supplementary to that of plasma angiotensins.

Adult↗
PubMed1989

Lithium clearance in water immersion-induced natriuresis in humans.

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Indomethacin increases renal lithium reabsorption in man.

We examined the effect of semi-acute indomethacin (4 x 50 mg orally during the preceding 27 h) on renal function parameters, including fractional lithium reabsorption (FRLi) in seven healthy subjects during a 200 mmol and a 40 mmol sodium diet. Studies were carried out during maximal water diuresis. During the sodium-rich diet, indomethacin raised minimal urine osmolality from 61 +/- 1 to 72 +/- 2 mosm/kg (P less than 0.05), and during the sodium-restricted diet from 55 +/- 3 to 93 +/- 6 mosm/kg (P less than 0.01). Indomethacin reduced maximal free water clearance only during the low-sodium diet, and had no consistent effect on inulin clearance and the fractional excretions of sodium, phosphate and uric acid. Nevertheless, FRLi rose substantially, from 71 +/- 2% to 75 +/- 2% (P less than 0.01) and from 75 +/- 2% to 81 +/- 2% (P less than 0.01) during high- and low-sodium diets respectively. During either diet, indomethacin caused a significant reduction of 24-h urine PGE2 excretion. Since indomethacin is not supposed to influence proximal tubular sodium reabsorption, the rise in lithium reabsorption occurred beyond this nephron level, presumably in the loop of Henle. Clearly, the FRLi cannot be used as a quantitative marker of proximal tubular sodium reabsorption in humans in all conditions.

Absorption↗