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Biomedical subjects

P Boer

Publications and source records attributed to P Boer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role of cellular ribose-5-phosphate content in the regulation of 5-phosphoribosyl-1-pyrophosphate and de novo purine synthesis in a human hepatoma cell line.

5-Phosphoribosyl-1-pyrophosphate (PRPP) is an important regulator of de novo purine synthesis. However, the role of ribose-5-phosphate (R5P), the precursor for PRPP, in the regulation of PRPP and de novo purine synthesis has not yet been clarified conclusively. This study was designed to clarify interrelationships between R5P content, PRPP availability, and the rate of de novo purine synthesis in the cultured human hepatoma cell line (HepG2), a plausible model for normal human hepatocytes. Increasing glucose concentration in the culture media from 0 to 10 mmol/L resulted in a 2.9-fold elevation of cellular R5P content (from 107 +/- 31 to 311 +/- 57 nmol/g protein), associated with a correlated increase of 7.14-fold in cellular PRPP availability (from 4.76 +/- 3.4 to 34 +/- 8.4 pmol/mg protein/min) and of 149-fold in the rate of de novo purine synthesis (from 55 to 8,204 dpm/mg protein/h). Plotting the rate of de novo purine synthesis versus R5P content indicates that at a wide range of R5P content, including that prevailing in hepatocytes under physiological conditions, the rate of purine synthesis depends on R5P content. A similar dependence was also demonstrated for PRPP availability. The rate of de novo purine synthesis exhibited a sigmoidal dependence on PRPP availability. The demonstration in human hepatocytes of dependence of the rate of purine synthesis on R5P content has implications concerning the pathogenesis of purine overproduction associated with several inborn and acquired conditions in man.

Carcinoma, Hepatocellular↗
PubMed1995

Efficacy of intrarenal ACE-inhibition estimated from the renal response to angiotensin I and II in humans.

Recent studies on the nature of the renin-angiotensin system (RAS) in animals have led to the concept that systemic and intrarenal RAS can be influenced to different degrees by angiotensin converting enzyme (ACE) inhibitors. Assessment of efficacy of intrarenal ACE inhibition by ACE inhibitors in humans is necessarily indirect and has not been reported. We therefore monitored the renal response to acute angiotensin (Ang) I infusion in volunteers taking 20 mg enalapril twice daily, and related the responses to the obtained increments in plasma Ang II levels. Ang I infusion rates of 4, 8, 16, and 32 pmol/kg/min caused gradual increments in plasma Ang I (maximal change from 26 +/- 18 to 578 +/- 120 pmol/liter, P < 0.05) and, despite treatment with enalapril, also of Ang II (from 3 +/- 1 to 29 +/- 5 pmol/liter, P < 0.05). This was associated with large reductions in renal plasma flow (paraaminohippurate clearance), filtration fraction, maximal urine flow, sodium excretion, lithium and uric acid clearance, and increments in mean arterial pressure and plasma aldosterone (P < 0.05 for each variable). Strong correlations existed between the changes in either variable and the increment in plasma Ang II. Infusions of Ang II at 1 and 4 pmol/kg/min in the same subjects caused comparable increments in plasma Ang II and had similar physiological effects as found during the Ang I infusion. Analysis of covariance of the changes in plasma Ang II and each of the measured variables revealed no differences between Ang I and Ang II infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of low-dose angiotensin II infusion on loop segment reabsorption: a free-flow micropuncture study in rats.

1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule. 2. Endogenous angiotensin II was suppressed by pretreatment with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 +/- 0.05 to 1.10 +/- 0.05 ml/min, Na+ excretion from 0.43 +/- 0.09 to 0.13 +/- 0.03 mumol/min, fractional delivery of water at the late proximal tubule from 50.1 +/- 1.7 to 42.9 +/- 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 +/- 1.3 to 39.1 +/- 3.5% and fractional delivery of water at the early distal tubule from 26.4 +/- 1.4 to 21.9 +/- 1.0% (P < 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly. 3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 +/- 0.7 to 6.8 +/- 0.9% (P < 0.05). 4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1995

Direct assessment of extracellular water volume by the bromide-dilution method in growth hormone-deficient adults.

Body composition and water content were assessed in 36 growth hormone deficient (GHD) patients (M:23, F:13) and 14 controls (M:7, F:7) using anthropometry, hydrodensitometry, bioelectrical impedance measurement and the bromide-dilution method, with which extracellular water volume can be measured directly. GHD patients, compared to controls, did not differ in extracellular water volume, in hydration state and water distribution. A higher BMI (P = 0.002) and a higher body fat mass (P < 0.0001) were found in the patients. Based on circumference measurements, the GHD patients had a higher waist/hip ratio (P = 0.0001). This study shows that GHD patients, in comparison with healthy controls, have a normal extracellular water volume. The finding that extracellular water volume is within the normal range in GHD patients may be clinically relevant as it is well known that in the first months after initiating GH-replacement therapy, most patients have signs and symptoms of excessive water retention.

Adult↗
PubMed1994

Effects of endothelin-1 on renal function in humans: implications for physiology and pathophysiology.

Elevated levels of the vasocontrictor peptide endothelin-1 have been demonstrated in various pathological conditions that are characterized by sodium retention and/or renal vasoconstriction, such as heart failure, hepatorenal syndrome, renal failure and during administration of cyclosporin and radiocontrast. In the present study we studied in seven healthy subjects the renal and endocrine effects of systemic administration of endothelin-1 (0.5, 1.0 and 2.5 ng/kg/min). During endothelin-1 infusion plasma levels rose from 3.2 +/- 0.5 to respectively 5.0 +/- 0.8, 6.2 +/- 0.5 and 8.5 +/- 1.1 pmol/liter, values that can also be observed in physiological and pathological conditions. Infusion of low dosages of endothelin-1, that result in a twofold increase in plasma levels, decreased sodium excretion by 36%, without a significant effect on systemic and renal hemodynamics. Infusion of 2.5 ng/kg/min of endothelin-1 further enhanced sodium retention and, in addition, increased renal vascular resistance by 37%. Blood pressure did not change significantly. Pretreatment with the calcium channel blocker nifedipine caused renal vasodilation, which compensated for the renal vasocontriction by endothelin-1 and prevented sodium retention. Apparently, endothelin-1 participates in volume homeostasis in human, whereas pathophysiological concentrations can contribute to renal vasoconstriction and sodium retention. Calcium channel blockers may protect against these effects of endothelin-1.

Adult↗
PubMed1994

Tubuloglomerular feedback and tubular reabsorption during acute potassium loading in rats.

Acute hyperkalemia has been associated with changes in reabsorption, glomerular filtration rate (GFR), and autoregulation, which might represent altered tubuloglomerular feedback (TGF) responsiveness. Therefore, TGF responsiveness, segmental reabsorption of water, sodium and potassium, and single-nephron GFR were evaluated during acute potassium loading in male Sprague-Dawley rats. Rats receiving 300 mM KNO3, KHCO3, and KCl showed significantly increased plasma potassium levels and attenuation of stop-flow pressure responses 45-90 min after starting the potassium infusion compared with that observed in time controls and rats infused with 300 mM NaCl. Attenuation of TGF responsiveness could not be related to plasma and kidney angiotensin II levels. Segmental water and sodium handling and proximal to distal single-nephron GFR differences assessed in a time control group and a group receiving 300 mM KCl revealed no changes related to KCl infusion. However, late proximal and early distal potassium concentrations increased significantly from 4.7 +/- 0.2 to 6.3 +/- 0.3 mM (P < 0.01) and from 1.5 +/- 0.1 to 2.7 +/- 0.4 mM (P < 0.01), respectively. In summary, although attenuated TGF responsiveness was demonstrated at higher perfusion rates, this study does not support a significant role for either the TGF mechanism or changes in reabsorption upstream of the early distal tubule for the initiation of kaliuresis during acute potassium loading.

Absorption↗
PubMed1994

The origin of urinary angiotensins in humans.

To examine whether urinary angiotensin (ANG) I and II excretion responds to changes in plasma ANG I and ANG II, ANG I or ANG II was infused in seven healthy subjects pretreated with a 340-mmol sodium diet and 20 mg of enalapril twice daily. Infusion rates were 4, 8, 16, and 32 pmol/kg per minute for ANG I and 1, 4, and 8 pmol/kg per minute for ANG II. Baseline ANG I and ANG II excretions averaged 10 and 20 fmol/min, respectively, which is approximately 0.3 and 5% of the filtered loads. Despite a 20-fold increase in plasma ANG I during ANG I infusion, urinary ANG I did not increase. Similarly, the 30-fold increase in plasma ANG II during ANG II infusion was not followed by an increase in ANG II excretion, but in fact by a decrease in urinary ANG I and ANG II. In a separate study, urinary ANG I and ANG II were measured before and after the oral administration of 20 mg of enalapril in eight healthy volunteers taking 400, 200, or 20 mmol of NaCl daily. In contrast to the considerable effects on plasma ANG I and ANG II and renal hemodynamics, enalapril had no effect on urinary ANG I and ANG II. Variation of sodium intake had predictable effects on plasma ANG I and ANG II but did not affect urinary ANG I and ANG II. These data suggest that urinary ANG I and ANG II originate from an intrarenal source. The independency of sodium intake and ANG-converting enzyme make the juxtaglomerular apparatus as the site responsible for the production of this ANG unlikely.

Adult↗
PubMed1993

Stimulation of calcitonin/CGRP-I and CGRP-II gene expression by dibutyryl cAMP in a human medullary thyroid carcinoma (TT) cell line.

In a human medullary thyroid carcinoma (TT) cell line, expression of the calcitonin (CT)/CT gene-related peptide (CGRP-I) gene (CALC-I or alpha) at the level of mRNA and of encoded peptides is higher than that of the closely related CGRP-II gene (CALC-II or beta). In response to 1 mM dibutyryl cAMP ((Bu)2cAMP), mature CGRP-II mRNA and intact cellular CGRP-II were raised 65- and 10-fold, respectively, at 72 h. Also at 72 h, 1 mM sodium butyrate enhanced CGRP-II mRNA only 9-fold and cellular CGRP-II 2-fold; stimulation of CGRP-I and CT mRNA and of cellular CGRP-I and CT by both (Bu)2cAMP and sodium butyrate was similarly low. During the same incubation time period secreted CGRP-II was raised 44-fold in response to (Bu)2cAMP, and CGRP-I and CT 8- and 42-fold, respectively. In conclusion, gene products of CALC-I (CGRP-I and CT) are present in higher amounts in TT cells than those of CALC-II (CGRP II). Yet (Bu)2cAMP predominantly stimulates the expression of CALC-II.

Bucladesine↗
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 enalapril on renal sodium handling in healthy subjects on low, intermediate, and high sodium intake.

Angiotensin-converting enzyme (ACE) inhibitors have a modest natriuretic effect, but the responsible changes in tubular sodium (Na) handling are not fully known. We therefore studied the effect of a single dose of 20 mg enalapril on Na excretion in 8 healthy subjects, using lithium clearance and maximal water diuresis to analyze tubular Na handling. Because the natriuretic effect may depend on the volume state, the same subjects were studied during low (20 mmol Na/day), medium (200 mmol Na/day), and high (400 mmol Na/day) salt intake. Enalapril caused natriuresis during the 20-mmol Na diet (from 51 +/- 9 to 81 +/- 14 mumol/min, p < 0.05) and the 200-mmol Na diet (from 190 +/- 24 to 230 +/- 31 mumol/min, p < 0.05), but not during the 400-mmol Na diet. The increase in Na excretion was not accompanied by consistent changes in glomerular filtration rate (GFR), free water clearance data, maximal urine flow, uric acid clearance, or lithium clearance. Instead, the increase in Na excretion was positively related to the increase in Na concentration in the maximally diluted urine (r = 0.75, p < 0.01). Regardless of diet, enalapril reduced the filtration fraction, but a significant increase in effective renal plasma flow was noted only during the 20-mmol Na diet. The data suggest that a decrease in Na reabsorption in the diluting segment, perhaps related to renal vasodilatation, participates in the natriuretic effect of ACE inhibition in humans.

Adult↗
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

Natriuretic and hypotensive effect of adenosine-1 blockade in essential hypertension.

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of acute mineralocorticoid and glucocorticoid receptor blockade on the excretion of an acute potassium load in healthy humans.

To examine the role of mineralocorticoid and glucocorticoid in potassium (K) tolerance in healthy humans, we studied the effects of canrenoate, a mineralocorticoid antagonist, and RU486, a glucocorticoid antagonist, on the excretion of a KCl load. Canrenoate (200 mg, iv) or RU486 (400 mg, orally) was administered 150 min before a KCl load (1 mmol/kg BW, orally) in seven healthy males undergoing maximal water diuresis. Clearance studies were extended for 5 h after the KCl load, and the data were compared with time control, KCl load alone, and canrenoate alone. KCl increased K excretion (from 18.8 +/- 2.4 to 63.3 +/- 3.9 mmol/5 h; P < 0.01) and sodium (Na) excretion (from 35.9 +/- 2.1 to 72.9 +/- 6.0 mmol/5 h; P < 0.01). Clearance calculations, based on maximal water diuresis, were compatible with increased distal Na and volume delivery. Canrenoate alone modestly increased basal cumulative NaCl excretion and had no effect on K excretion. However, canrenoate blunted the kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compared to KCl alone) and stimulated natriuresis in a complementary way. Clearance data were compatible with diminished distal Na reabsorption and K secretion in response to an undisturbed KCl-induced increase in distal Na delivery. RU486 did not influence the excretion of the KCl load or its effects on renal sodium handling parameters, although effective glucocorticoid receptor blockade was likely to be present in view of the increase in plasma cortisol. These data suggest that in healthy humans, mineralocorticoid activity, but not glucocorticoid activity, is involved in the elimination of a K load. The latter contrasts with data in adrenalectomized animals, in which situation glucocorticoid as well as aldosterone are indispensible for normal K tolerance.

Administration, Oral↗
PubMed1992

Effects of angiotensin II on renal sodium handling and diluting capacity in man pretreated with high-salt diet and enalapril.

The antinatriuretic effect of angiotensin II (Ang II) is generally attributed to a decreased glomerular filtration rate (GFR) and an increased proximal tubular sodium reabsorption. We studied this by infusion of increasing amounts (1, 4, and 8 pmol/kg per min) of Ang II in seven water-loaded volunteers who were pretreated with enalapril and a high-salt diet. While mean arterial pressure increased from 92 +/- 3 mmHg to respectively 98 +/- 3, 110 +/- 2, and 116 +/- 2 mmHg, sodium excretion fell from 331 +/- 40 to 135 +/- 23, 65 +/- 17, and 63 +/- 22 mumol/min, and GFR from 138 +/- 9 to 128 +/- 6, 111 +/- 6, and 104 +/- 8 ml/min (P < 0.05 for each variable). At 1 pmol/kg per min, Ang II decreased maximal urine flow and the fractional excretions of lithium and uric acid. Urine sodium concentration decreased, whereas minimal urine osmolality remained unchanged. At 4 pmol/kg per min, these effects were more pronounced. Moreover, minimal urine osmolality increased from 58 +/- 4 to 72 +/- 8 mosm/kg, but sodium concentration decreased further. The step to 8 pmol/kg per min did not decrease sodium, lithium, or uric acid excretion further, but induced a further increase in minimal urine osmolality to 99 +/- 16 mosm/kg. These data suggest that the antinatriuretic effect of modestly hypertensive dosages of Ang II is not only due to a decrease in GFR and an increase in proximal sodium reabsorption, but also involves a rise in fractional reabsorption in a distal nephron segment. In addition Ang II decreases renal diluting capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗