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P Boer

Publications and source records attributed to P Boer.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1991

Response of urinary angiotensin to challenges of the renin-angiotensin system.

Angiotensin has an intrarenal action which may not parallel its action in the general circulation. We investigated whether the urinary excretion rates of angiotensin I and II (UV-AI, UV-AII) can be used as a marker of renal production. We therefore measured UV-AI, UV-AII, plasma angiotensin I and II (PAI, PAII), and plasma renin activity (PRA) in healthy subjects under conditions influencing the renin-angiotensin system: captopril injection (n = 7), enalapril treatment (n = 9), furosemide infusion on high and low sodium intake (n = 6), indomethacin treatment (n = 8), and head-out water immersion (three sodium intakes). After captopril (acute) and enalapril (chronic), PAI and PRA increased, PAII decreased, but neither UV-AI nor UV-AII changed. During furosemide infusion, PAI, PAII, PRA, as well as UV-AI and UV-AII increased. During indomethacin treatment, PAI, PAII, and PRA decreased, whereas UV-AI and UV-AII did not change consistently. Sodium restriction increased PAI, PAII, and PRA, but did not alter UV-AI and UV-AII. Head-out immersion decreased PAI, PAII, and PRA, but did not change UV-AI and UV-AII. The relative constancy of the urinary AI and AII excretion rates makes it doubtful whether urinary angiotensins reflect changes of renal angiotensin production.

Adult↗
PubMed1991

Hemodynamic effects of Ro 23-6152 in patients with essential hypertension.

In a double blind study 8 patients with uncomplicated essential hypertension received in random order single oral doses of placebo and 10, 30 and 80 mg Ro 23-6152, a novel calcium entry blocker, on 4 different days. Patients were assessed 15 min before dosing and at several time intervals over the following 6 h. Ro 23-6152 30 and 80 mg induced a significant decrease (mean maximum 7 mmHg.1-1.min-1) in total peripheral resistance, while cardiac output, stroke volume and heart rate were slightly increased (mean maximum 0.51.min-1, 10 ml, 5 beats.min-1, respectively) but not significantly so. Systolic blood pressure decreased significantly (5 to 10 mmHg) from 0.5 to 6 h after the 80 mg dose. After the 10 and 30 mg doses the decreases in systolic pressure were not significant. Diastolic blood pressure and mean arterial blood pressure were non-significantly decreased (mean maximum 7 mmHg) after all doses. The PQ interval was also non-significantly increased by no more than 20 ms. It appears that the main hemodynamic effect of Ro 23-6152 in hypertensive patients is a decrease in peripheral resistance. The antihypertensive effect, at least in this short term study, was only modest, probably because the fall in peripheral resistance was partly compensated by an increase in cardiac output.

Adult↗
PubMed1991

Stimulation of ribose-5-phosphate and 5-phosphoribosyl-1-pyrophosphate generation by pyrroline-5-carboxylate in mouse liver in vivo: evidence for a regulatory role of ribose-5-phosphate availability in nucleotide synthesis.

Pyrroline-5-carboxylase (P5C), a physiological stimulator of hexose-monophosphate-pentose pathway activity, was found before to increase 5-phosphoribosyl-1-pyrophosphate (PRPP) generation and nucleotide synthesis in human erythrocytes and cultured fibroblasts. We now report the stimulation of PRPP generation by P5C also in mouse liver in vivo. In addition we demonstrated a simultaneous elevation in ribose-5-phosphate (R5P) concentration, which was relatively smaller and transient. The demonstrated effect of P5C on liver R5P and PRPP content in vivo provides strong evidence for the physiological role of R5P availability in the regulation of PRPP and purine production.

Animals↗
PubMed1991

Acceleration of purine synthesis in mouse liver by glycogenolytic hormones.

Administration (ip) into fed mice of glucagon, epinephrine, vasopressin, oxytocin, angiotensin II, and dibutyryl cyclic AMP (dbcAMP) resulted in a rapid (within 2.5 to 15 min) elevation of PRPP content (two- to threefold) and in acceleration of the rate of de novo purine synthesis (twofold). Inhibition of the epinephrine-stimulated glycogenolysis by 2,5-anhydromannitol diminished markedly the acceleration effect of the hormone on the rate of purine synthesis. Administration of the hormones caused a rapid rise in the liver content of glucose 6-phosphate (G6P) by 15-70% but did not increase the ribose 5-phosphate (R5P) content. Liver ATP content was not affected. The hormones did not cause direct activation of PRPP synthetase, as gauged by the specific activity of the enzyme, its Km for substrates R5P and ATP, and its sensitivity to inhibition by ADP and GDP. The hormones did not increase the liver content of the enzyme activators Pi and Mg2+. The results suggest that the glycogenolytic hormones accelerate purine synthesis by a metabolic mechanism associated with the enhancement of glycogenolysis. PRPP synthesis is probably enhanced by the glycogenolysis-induced alterations in the cellular content of some metabolites other than R5P.

Animals↗
PubMed1989

Blunted natriuretic response and low blood pressure after atrial natriuretic factor in early cirrhosis.

We compared the natriuretic response to a standard dose of atrial natriuretic factor in nine patients with early cirrhosis (no ascites or edema) with the response in normal subjects displaying a range of baseline sodium excretions due to different sodium intakes (20 mmoles per day, n = 9; 100 mmoles per day, n = 9, and 200 mmoles per day, n = 9). In these normal subjects, sodium output rose, in the same order, from 49 +/- 12 to 177 +/- 26, from 116 +/- 21 to 365 +/- 106 and from 228 +/- 29 to 901 +/- 85 mumoles per min in the first 20 min after 100 micrograms atrial natriuretic factor (human atrial natriuretic factor 99-126). Thus, irrespective of basal excretion, natriuresis rose by at least 2-fold. In the cirrhotic patients, natriuresis rose from 173 +/- 42 to 305 +/- 77 mumoles per min, that is by hardly 1-fold, significantly less than in the normal subjects (p less than 0.01). Renal function studies indicated that atrial natriuretic factor caused less rise in glomerular filtration rate and in fractional sodium excretion. Atrial natriuretic factor induced a fall in blood pressure only in the cirrhotic group, from 130 +/- 4/81 +/- 2 to 108 +/- 4/68 +/- 3 mmHg (p less than 0.001). Plasma atrial natriuretic factor was not low in the cirrhotic patients. Although these data are compatible with a primary disturbance of sodium excretion in early cirrhosis without ascites, such an explanation is complicated by the concomitant drop in blood pressure after atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Renal response to infusion versus repeated bolus injections of atrial natriuretic factor in man.

In 7 healthy humans consuming a 170 mmol sodium diet the effect of the mode of administration of atrial natriuretic factor (human ANF 99-126) on renal function has been investigated, using conventional clearance studies during maximal water diuresis. ANF was administered as four repeated bolus (0.4 microgram/kg) injections and, after a 2-day interval, as a one-hour infusion (0.02 microgram/kg/min) preceded by a 0.4 microgram/kg bolus injection. In the two experiments ANF caused comparable elevations in glomerular filtration rate, free water clearance, and lithium excretion. No change in blood pressure or heart rate was observed in either study, and plasma renin activity and aldosterone fell by a similar extent. As expected, the time course of plasma ANF concentrations was markedly different during the two studies. It is concluded that with those doses of ANF the changes in renal haemodynamics and sodium handling were essentially similar after bolus injections and a constant infusion.

Adult↗
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

Role of ANP in natriuresis of head-out immersion in humans.

Atrial natriuretic peptide (ANP) may play a role in the natriuresis after acute circulatory challenges. To assess this role in head-out water immersion (HOI), we compared in clearance studies the effect of 3 h HOI with an equally natriuretic 3-h infusion of ANP [0.01 microgram.kg-1.min-1 human ANP-(99-126)] in seven healthy individuals taking a 100 mmol sodium diet. The studies were repeated after treatment with enalapril (20 mg twice daily), which in previous studies inhibited the natriuresis after ANP. HOI caused a natriuresis equal to that of ANP infusion despite an about five times smaller rise in plasma ANP. HOI increased and ANP decreased estimated renal plasma flow (ERPF). HOI increased maximal free water clearance and decreased fractional lithium reabsorption. ANP did not affect these variables but raised minimal urine osmolality. Enalapril enhanced the fall in ERPF caused by ANP and abolished its natriuretic effect; enalapril did not impair either the natriuresis after HOI or the increase in ERPF and the fall in lithium reabsorption. These data indicate that the low dosage of ANP causes natriuresis by reducing sodium absorption in a distal nephron target segment; enalapril impairs this effect, perhaps by enhancing ANP-induced vasoconstriction, which decreases delivery to this target segment. HOI, by increasing sodium delivery to this segment, is natriuretic despite only a small rise in plasma ANP. Enalapril does not impair these effects. Although a rise in plasma ANP may be one factor in the natriuresis of HOI, the present data speak against an exclusive role. Other factors determine the magnitude of the natriuretic response.

Adult↗
PubMed1989

Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans.

In clearance studies, we analyzed the effect of Ca2+ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 micrograms bolus followed by an infusion of 0.03 microgram/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca2+ entry blockade or converting enzyme inhibition. Natriuresis rose from 239 +/- 38 to 605 +/- 137 mumol/min in the control study (p less than 0.05), from 330 +/- 53 to 943 +/- 152 mumol/min with Ca2+ entry blockade (p less than 0.05), and from 236 +/- 22 to 344 +/- 39 mumol/min with converting enzyme inhibition (NS). ANF induced a rise in maximal free water clearance, inulin clearance, and in the excretion of multiple electrolytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca2+ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca2+ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p less than 0.05 vs. control and vs. Ca2+ entry blockade study). Blood pressure was lowered by Ca2+ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca2+ entry blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Mineralocorticoid activity and the excretion of an oral potassium load in normal man.

In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of these drugs. A steep positive relation between plasma K (ordinate) and urine K or Na (abscissa) was found, compatible with a strong influence of changes in plasma K on K and Na excretion. Fludrocortisone reset the relation to a lower level of plasma K. Spironolactone, on the other hand, had little effect on these relations, although a tendency towards a higher plasma K could be recognized. Paradoxically, the K load was excreted less efficiently during fludrocortisone, probably due to enhanced cellular K deposition. Prolonged kaliuresis relative to the transient rise in plasma K and natriuresis was found only without medication. Only in this situation aldosterone rose and fell parallel to plasma K. We conclude that: 1) chronic mineralocorticoid increase shifts the set point of both K and Na excretion following a K load to a lower plasma K, compatible with resetting of the positive influence of plasma K on distal solute delivery towards a lower plasma K; 2) total kaliuresis is paradoxically low due to enhanced cellular K uptake; 3) blockade of endogenous aldosterone action has relatively little influence on these relations between plasma K and urine K or Na; 4) the contribution of acute aldosterone stimulation to the excretion of a single oral K load can be recognized as a delayed kaliuresis extending beyond the peak in plasma K.

Adult↗
PubMed1988

Unimpaired excretion of an acute salt load in conscious hypoproteinaemic dogs.

1. The role of hypoproteinaemia in the sodium retention seen in conditions such as the nephrotic syndrome is incompletely known. 2. To define the influence of severe hypoproteinaemia on kidney function, we studied the effect of an intravenous infusion of an isotonic saline load (133 mmol of sodium), as 1 litre of Ringer lactate solution, on sodium excretion and renal haemodynamics in conscious dogs before and after reduction of plasma protein from 68 +/- 3 to 36 +/- 2 g/l by repeated plasmapheresis and a low protein diet. 3. During hypoproteinaemia, 2 days after a period of plasmapheresis, glomerular filtration rate and effective renal plasma flow were lower than in the control study. After the sodium load, both rose to values nearly identical with the pre-infusion levels found in normoproteinaemia, the filtration fraction remaining unchanged. This contrasted with the rise in filtration fraction after expansion in normoproteinaemia, where filtration fraction increased from 32 to 39% due to a rise in glomerular filtration rate. 4. After expansion, natriuresis rose to similar levels in normoproteinaemia (0.18 +/- 0.06 mmol/min) and hypoproteinaemia (0.20 +/- 0.06 mmol/min), and increments in fractional excretion of sodium, potassium and chloride were also similar. However, baseline excretion was higher in the hypoproteinaemic dogs due to their overhydrated condition in this period immediately after plasmapheresis. 5. The fractional excretion of lithium, an alleged marker of proximal tubular sodium reabsorption, rose to comparable levels. 6. Hence, both the increase in filtration and decrease in reabsorption of sodium after an isotonic saline load are not affected by severe reduction in plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Heterozygotes for 17 alpha-hydroxylase deficiency can be detected with a short ACTH test.

A short ACTH test was performed in the six parents, and four siblings, of three cases with 17 alpha-hydroxylase deficiency. Baseline steroid levels were all normal in female heterozygotes but in males 17 alpha-hydroxyprogesterone levels were elevated. After ACTH-stimulation, plasma levels of corticosterone were elevated in five obligate heterozygotes and 18-hydroxydeoxycorticosterone levels were increased in four of them. Two of the four siblings had biochemical signs of heterozygosity. The short ACTH test appears to be an efficient method for detecting heterozygosity, but the abnormalities found are more heterogeneous than previously suggested.

Adolescent↗
PubMed1988

Hypoproteinemia and recovery from edema in dogs.

We studied the effects of hypoproteinemia following 12 days of repeated plasmapheresis and low-protein diet on sodium balance, fluid volumes, and renal hemodynamics in six conscious dogs on 50 mmol sodium intake. Measurements during hypoproteinemia were obtained during a 5-day recovery period starting 20 h after the final plasmapheresis session, with continued low-protein diet. During the plasmapheresis period sodium was retained. Sodium balance became negative on the first recovery day when plasma protein was 29 +/- 1 g/l (control 60 +/- 2 g/l, P less than 0.01), and plasma colloid osmotic pressure (COP) was 9 +/- 1 mmHg (control 22 +/- 1 mmHg, P less than 0.01). Subcutaneous fluid COP was lowered from 14 +/- 1 to 4 +/- 1 mmHg (P less than 0.01). Blood volume, plasma renin activity, and aldosterone were unchanged. Glomerular filtration rate and effective renal plasma flow were slightly reduced (NS), and filtration fraction was unchanged. After a second plasmapheresis period in three of the dogs, plasma protein fell to 26 +/- 1 g/l and COP to 7 +/- 1 mmHg. Now sodium was retained on the first day after stopping plasmapheresis, and renin and aldosterone were high. The next day, when plasma protein was again 29 +/- 1 g/l and COP 8 +/- 1 mmHg, these three dogs were able to completely excrete an infusion of 130 mmol sodium. These data suggest that the level of plasma COP below which dogs on a medium-sodium intake would retain sodium averages 8 mmHg, which is considerably lower than generally thought.

Animals↗