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Biomedical subjects

W H Boer

Publications and source records attributed to W H Boer.

48 records · Page 3Linked to original sources
PubMed1988

Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve.

Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.

Cardiovascular System↗
PubMed1988

Renal lithium handling during water loading and subsequent d-DAVP-induced anti-diuresis.

Assuming that lithium is exclusively reabsorbed in the proximal tubules pari passu with sodium (Na), the lithium clearance (CLi) has been advanced as an index of filtrate delivery from the proximal tubules. In order to determine whether water loads in a range commonly given during clearance studies affect CLi, we studied nine normal subjects (Na intake 150 mmol day-1) on three water loads resulting in stable urine flow rates of 2.2 +/- 0.9, 6.1 +/- 0.7 and 11.7 +/- 3.0 ml min-1, respectively. We also studied the effect of acute anti-diuresis (urine flow less than 1 ml min-1) induced by d-DAVP given i.v. at the end of all studies. Water loading up to induction of maximum water diuresis did not significantly affect absolute or fractional CLi. Sodium and chloride excretion were reduced at the highest water intake level. Administration of d-DAVP caused a 50% reduction in fractional Na excretion and a small but significant rise in fractional lithium reabsorption from 75.5 +/- 3.9 to 77.5 +/- 3.6%. We conclude that CLi is hardly affected over a wide range of water intakes and urine flow rates, despite concomitant changes in Na excretion. The finding that d-DAVP, which probably enhances Na reabsorption in the thick ascending limb of Henle's loop, also enhanced lithium reabsorption, suggests that lithium may be partly reabsorbed in this nephron segment. Thus, lithium may not be the exact, quantitative marker of Na reabsorption in the proximal tubules that it is purported to be.

Deamino Arginine Vasopressin↗
PubMed1988

Lithium clearance during variations in sodium intake in man: effects of sodium restriction and amiloride.

Assuming that lithium is exclusively reabsorbed in the proximal tubules in proportion to sodium and water, the lithium clearance (CLi) has been advanced as an index of filtrate delivery from the proximal tubules. However, studies in the rat and dog showed that CLi drops sharply at fractional sodium excretion rates (FENa) below 0.4% due to lithium reabsorption in the amiloride-sensitive segment of the distal nephron, which disqualified CLi as an index of distal filtrate delivery during sodium restriction in these animals. In order to investigate whether this phenomenon also occurs in man, we studied CLi in 103 normal subjects at varying sodium intakes, including marked sodium restriction. In contrast to findings in the rat and dog, no sharp drop but a gradual fall in CLi was observed at decreasing FENa values down to 0.02%. Maximum urine flow, another index of filtrate delivery from the proximal tubules, decreased proportionally, suggesting that the fall in CLi was due to enhanced proximal and not distal lithium reabsorption. Amiloride (15 mg p.o.) did not affect CLi despite unequivocal effects in the distal nephron in eight normal subjects at a mean FENa of 0.1%. In conclusion, a low FENa due to severe sodium restriction in man is not accompanied by strongly enhanced distal lithium reabsorption sensitive to amiloride. Thus, in contrast to the rat and dog, a low FENa forms no objection to use CLi as an index of sodium and filtrate delivery from the proximal tubules in humans.

Amiloride↗
PubMed1987

Lithium clearance during the paradoxical natriuresis of hypotonic expansion in man.

Tubular sodium handling in humans undergoing hypotonic expansion due to the administration of antidiuretic hormone was studied using the clearance of lithium as an index of distal filtrate and sodium delivery. Clearance studies were performed in the morning in eight normal subjects before and on the fourth day of intranasal I-desamino-8-D-arginine vasopressin (dDAVP) administration. Fluid intake was kept constant at 25 ml/kg body weight. After dDAVP body weight increased (2.5 +/- 0.4 kg), plasma sodium fell (from 143 +/- 1 to 128 +/- 5 mmol/liter) and a progressive natriuresis developed. Sodium balance remained negative up to the second clearance study, when the cumulative sodium loss amounted to 148 +/- 96 mmol. Plasma renin activity fell significantly, but plasma aldosterone did not. Inulin clearance rose from 110 +/- 14 to 135 +/- 23 ml/min and lithium clearance from 30.9 +/- 7.6 to 48.9 +/- 15.1 ml/min. Fractional reabsorption of uric acid, phosphate and calcium decreased. Together these changes suggest that the negative sodium balance in hypotonic expansion with dDAVP results from increased filtered sodium load, decreased fractional reabsorption in the proximal tubules, and increased distal delivery. Estimated fractional reabsorption in the distal nephron remained unaltered. The plasma concentration of lithium, of which 10.8 mmol was ingested on the eve of the clearance studies, was not lower during the dDAVP-clearance study. This indicates that the tubular adaptations mentioned are present intermittently, in particular during daytime.

Absorption↗
PubMed1987

Renal haemodynamics and sodium handling after hyperoncotic albumin infusion in sodium-restricted normal man.

The effect of plasma volume expansion with hyperoncotic albumin (HA) on renal haemodynamics and segmental tubular sodium (Na) handling was studied in eight water-loaded normal men. Clearance studies were performed before, during and after a 60-min infusion of 300 ml 20% HA. Sodium intake was restricted (20 mmol day-1) to mimic clinical conditions of relative hypovolaemia in which HA is often applied. Plasma volume rose by 740 +/- 160 ml after infusion and colloid oncotic pressure (COP) by 3.6 +/- 1.3 mm Hg. No natriuresis was induced. In fact, Na output fell from 43 +/- 29 to 28 +/- 25 mumol min-1 during infusion, returning to 41 +/- 36 mumol min-1 afterwards. Corresponding clearances of inulin were 121 +/- 19, 110 +/- 19 and 117 +/- 21 ml min-1 and of p-aminohippurate (CPAH) 602 +/- 87, 637 +/- 100 and 751 +/- 148 ml min-1. Fractional reabsorption of sodium in the proximal tubules (FPRNa), assessed from maximal free-water and lithium clearance, rose consistently during infusion but diverging patterns (further rise, no change or fall) were seen afterwards. Fractional distal reabsorption remained unchanged both during and after HA infusion. Changes in plasma volume and CPAH in the post-infusion period were correlated. These results indicate that, despite considerable plasma volume expansion, HA infusion does not enhance Na excretion in Na-restricted subjects. This is mainly due to elevation of plasma COP, which reduces glomerular filtration and enhances proximal reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Lithium clearance in mineralocorticoid escape in humans.

Lithium clearance (CLi) has been advanced as an indicator of Na delivery from the proximal tubules. We studied CLi in eight healthy males before and after mineralocorticoid escape, a maneuver that may induce suppression of fractional proximal Na reabsorption (FPRNa). FPRNa was also estimated from changes in maximal free water clearance (CH2O). According to the latter method, FPRNa dropped from 85.7 +/- 2.2 to 81.3 +/- 3.4%, whereas inulin clearance rose from 125 +/- 11 to 149 +/- 15 ml/min. The changes in CLi were surprisingly large, from 40.6 +/- 7.6 to 75.8 +/- 18.4 ml/min. If lithium is a valid marker of Na handling in the proximal tubule in humans, this change would imply a fall in FPRNa from 67.5 +/- 3.9 to 49.7 +/- 9.0%, suggesting a much larger shift in tubular Na reabsorption in escape than hitherto suspected. In addition, it would suggest that the inevitable back diffusion of a part of the solute-free water in the distal nephron, and thus overestimation of FPRNa by the CH2O method, increases importantly during escape. Alternately, lithium may not be a good marker of proximal tubular Na handling. For instance, both lithium reabsorption and escape may take place beyond the proximal tubule, or lithium may be excreted in the distal nephron in certain conditions. Present methods do not permit further analysis of these options in the human model.

Adult↗
PubMed1987

Decreased lithium clearance due to distal tubular lithium reabsorption in sodium-depleted dogs.

Lithium clearances were performed in conscious dogs on varying sodium intakes. Fractional lithium excretion (FE-Li) was 22.6 +/- 2.2% in sodium-replete dogs (fractional sodium excretion, FE-Na greater than 0.4%, n = 11) but only 6.9 +/- 2.3% in sodium-depleted dogs (FE-Na less than 0.4%, n = 25). In 4 markedly sodium-depleted dogs (FE-Na 0.03 +/- 0.02%) the distally acting diuretic amiloride caused an 8-fold increase in FE-Li (from 1.5 +/- 1.0 to 11.6 +/- 2.0%). Our data suggest that tubular reabsorption of lithium in sodium-depleted dogs is not restricted to the proximal tubules but also occurs in the distal nephron. Therefore the lithium clearance cannot be used as an index of sodium and filtrate delivery from the proximal tubules in sodium-depleted dogs.

Amiloride↗
PubMed1987

Renal function during recovery from minimal lesions nephrotic syndrome.

We followed renal function through the natriuretic phase of 6 occasions of drug-induced recovery from minimal lesions nephrotic syndrome (MLNS). Protein excretion started to fall 1-3 days prior to the start of the natriuresis. The natriuresis was accompanied by a rise in glomerular filtration rate (GFR, inulin clearance). The filtration fraction, calculated from the GFR and the p-aminohippurate clearance, rose steadily in 5 subjects in whom it was low before therapy. Proximal and distal sodium reabsorption fractions, estimated from the changes in maximum free water clearance, fell, and fractional sodium, lithium, uric acid and free water clearance rose. At the time of these changes plasma protein had hardly risen, whereas renin activity was down. These results are in agreement with the notion that the sodium retention of MLNS is due to a renal defect. Repair of the glomerular filter, evident from the disappearance of proteinuria and the rise in filtration fraction, apparently normalizes the elevated tubular sodium reabsorption proximal to the macula densa, which leads to a fall in renin release.

Adolescent↗
PubMed1984

Nonselective beta-blockade enhances pressor responsiveness to epinephrine, norepinephrine, and angiotensin II in normal man.

Nonselective beta-blockers increase peripheral vascular resistance and, sometimes, blood pressure (BP); increased responsiveness to circulating pressor agents could be one of the underlying mechanisms. Heart rate (HR) and BP responses to graded intravenous infusions of epinephrine, norepinephrine, and angiotensin II were recorded after placebo and then after 4 wk of beta-blocker treatment (nadolol or propranolol, 240 mg/day) in 10 healthy young men. Adequacy of beta-blockade was demonstrated by a mean 31% decrease in HR response to bicycle exercise, with no differences between the two beta-blockers. Under placebo conditions epinephrine lowered diastolic BP and raised HR; these effects were reversed during treatment with beta-blockers. beta-Blockade potentiated BP responses to norepinephrine and angiotensin II: Thirty-five percent less norepinephrine and 52% less angiotensin II were required to increase mean BP by 15 mm Hg. A final study 2 wk after beta-blocker cessation revealed the absence of lasting effect. These results confirm the concept of unopposed alpha-constriction for epinephrine and also demonstrate increased BP responses to norepinephrine and angiotensin II during chronic beta-blockade.

Adult↗
PubMed1983

Diuretic and cardiovascular effects of indapamide in hypertensive subjects: a dose-response curve.

In a single-blind, placebo-controlled study, the effects were evaluated of increasing doses of indapamide (1.0, 2.5 and 5.0 mg/day, each dose for 4 weeks) on volume and haemodynamic status of 10 hypertensive subjects. Body weight showed a decrease of 0.5 kg at the 1 mg dose, of 1.0 kg at the 2.5 mg dose and no further decrease at 5 mg. Plasma volume did not change. Mean arterial pressure decrease in 8 subjects by about 20 mmHg; 2 patients were classified as 'non-responders'. The decrease in blood pressure was accompanied by a reduction in total peripheral resistance and no change in cardiac output. LV end-diastolic volume decreased by about 20 ml. These results suggest that indapamide not only has a diuretic effect, but also acts as a veno-arterial vasodilator.

Adult↗