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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 181 records · Page 10Linked to original sources
PubMed1992

Glomerular and tubular antinatriuretic actions of low-dose angiotensin II infusion in man.

OBJECTIVE: The aim was to study the physiological effects of angiotensin II upon the glomerular and tubular handling of sodium. DESIGN: Healthy volunteers were examined before and during infusion with either low-dose angiotensin II (n = 11) or placebo (n = 13). METHODS: Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. RESULTS: During infusion with angiotensin II a sustained and marked fall in renal plasma flow was observed. The glomerular filtration rate (GFR) decreased to a minor extent so that the filtration fraction increased during angiotensin II infusion. Angiotensin II caused an extensive and instantaneous fall in both urinary flow and urinary sodium excretion. Proximal absolute reabsorption of sodium was unchanged despite the fall in GFR, showing that proximal fractional reabsorption was enhanced by angiotensin II. Distal absolute reabsorption was decreased during the entire period of angiotensin II infusion. However, when the distal reabsorption was related to the delivery of sodium from the proximal tubules, distal fractional reabsorption in fact increased after 30 min angiotensin II infusion. None of the measured parameters changed during infusion with placebo. A significant increase in plasma aldosterone was observed 30 min after the start of the angiotensin II infusion. Plasma atrial natriuretic peptide did not change during infusion with either angiotensin II or placebo. CONCLUSIONS: We conclude that physiological increments in angiotensin II affect glomerular haemodynamics and cause a marked antinatriuresis in man. The antinatriuretic effect of angiotensin II is caused initially by a combination of a decrease in the GFR and an increase in proximal fractional sodium reabsorption, and later by the enhanced distal fractional reabsorption of sodium.

Adult↗
PubMed1992

Combined actions of isradipine and captopril on renal function in hypertension.

The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Interaction between cyclosporine and felodipine in renal transplant recipients.

The nephrotoxic adverse effect of cyclosporine in renal transplantation may be counteracted by calcium antagonists. The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was studied in ten cyclosporine-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporine in a randomized, single-blind crossover study. Glomerular filtration rate, and renal plasma flow, and tubular function evaluated by the lithium clearance technique were determined. Both glomerular filtration rate, renal plasma flow, urinary sodium excretion, fractional excretion of sodium, and lithium clearance increased after felodipine, whereas proximal and distal fractional reabsorption and blood pressure were reduced. Intravenous infusion of cyclosporine per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporine-treated renal transplant recipients has beneficial effects on renal hemodynamics, tubular function and blood pressure. It is suggested that these effects result from a direct vasodilatation and an effect on tubular function, and that felodipine given intravenously seems to antagonize at least some of the nephrotoxic effects of cyclosporine.

Adult↗
PubMed1991

Synthesis of 3'-amino-2',3'-dideoxy-hexofuranose nucleosides with potential anti-viral activity.

Michael type addition of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) phthalimide salt to 4,6-di-O-acetyl-2,3-dideoxy-aldehydo-D-erythro-trans-hex-2-enos e 2 and concomitant acetyl shift give an anomeric mixture of arabino and ribo isomers of 5,6-di-O-acetyl-2,3-dideoxy-3-phthalimido-D-hexofuranose 3 which after acetylation at the anomeric hydroxy group is separated to give 4 and 5. Subsequent reaction with 5'-substituted silylated uracil in the presence of TMS-triflate results in three different 5',6'-di-O-acetyl-2',3'-dideoxy-3'-phthalimido-D-hexofuranose nucleosides 7, 9, and 10 which were deprotected to give the corresponding 3'-amino nucleosides 8, 11, and 12. The compounds 7-12 were investigated for their activity against HSV-1 and HIV-1.

Animals↗
PubMed1991

Free-radical synthesis of 3-(2-cyanoethyl)- and 3-(2-methoxycarbonylethyl)-2,3-dideoxy-alpha-D-erythro-pentofu ranoside and their application in the synthesis of potential antiviral nucleosides.

Free-radical reaction of different carbohydrate educts 2, 5, and 7 with acrylonitrile in the presence of tributyltin hydride and a radical initiator (AIBN) gave the methyl 3-(2-cyanoethyl)-2,3-dideoxypentofuranosides 3a and 6. Similar reaction of 2 with methyl acrylate gave 3-(2-methoxycarbonylethyl)-2,3-dideoxypentofuranose 3b. Nucleoside coupling of 3a with silylated uracil gave an anomeric mixture of beta- and alpha-nucleoside 8 and 9 which were deprotected to give 10 and 11, respectively. Similar reaction of 3b with silylated N4-isobutyrylcytosine gave 12 and 13 which were deprotected to give the final nucleosides 16 and 17, respectively. None of the compounds 10a, 11, 14-17 showed significant activity against HIV.

Antiviral Agents↗
PubMed1991

Long-term treatment of nocturnal enuresis with desmopressin. A follow-up study.

Eight patients with monosymptomatic nocturnal enuresis (age 11-24 years) were investigated prior to and after 24 weeks of desmopressin treatment in order to evaluate the impact on the endogenous vasopressin secretion and urinary output. No effect on plasma vasopressin, diurnal urinary volume, and urinary osmolality were found after this long-term treatment. Overall no changes in either body weight, blood pressure, or hematological variables were demonstrated. This supports previous findings that the treatment appears to be well tolerated and free of side effects in longer term.

Adolescent↗
PubMed1991

Renal and hormonal effects and tolerance of an ANP analogue in healthy man.

The effect of an analogue of atrial natriuretic peptide (P-ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by the lithium clearance technique, and plasma levels of sodium and water homeostatic hormones, has been studied in 40 healthy males. Placebo or P-ANP 0.3, 1.5, or 3.0 micrograms.kg-1 bwt were given as an intravenous bolus injection to different groups. P-ANP did not cause any immediate change in GFR or RPF, but significant dose-dependent increases in filtration fraction, urinary flow rate and urinary excretion rate of sodium were detected during the first 30 min after administration. Proximal absolute and fractional tubular reabsorption and distal absolute tubular reabsorption of sodium did not change after injection of P-ANP, while the distal fractional reabsorption of sodium was reduced in a dose dependent manner during the first 30 min. Plasma angiotensin II and aldosterone were significantly increased 30 and 150 min after dosage, whereas plasma atrial natriuretic peptide, plasma arginine vasopressin, and urinary excretion of prostaglandin E2 were unchanged. Cyclic guanosine monophosphate both in plasma and urine were increased in a dose-dependent manner. P-ANP cause a significant reduction in diastolic blood pressure and an increase in pulse rate. Two subjects had vasovagal syncope 30-60 min after injection of P-ANP. It is concluded that P-ANP has natriuretic, diuretic and hypotensive properties in healthy man.

Adult↗
PubMed1991

Leukocyte infiltration and glial reactions in xenografts of mouse brain tissue undergoing rejection in the adult rat brain. A light and electron microscopical immunocytochemical study.

Neural mouse xenografts undergoing rejection in the adult recipient rat brain were characterized with regard to infiltrating host leukocytes and reactions of graft and host astro- and microglial cells. Rejection occurred within 35 days with infiltration of the grafts by in particular macrophages and T-cells as well as blood-brain barrier (BBB) leakage for IgG. In the surrounding host brain microglial cells showed increased histochemical staining for nucleoside diphosphatase (NDPase) and increased immunocytochemical expression of complement receptor type 3 (CR3), while astroglial cells displayed an increased immunoreactivity for glial fibrillary acidic protein (GFAP). Light microscopic findings of rat major histocompatibility complex (MHC) antigen class I on microglial cells, endothelial cells and leukocytes were confirmed at the ultrastructural level and extended to include a few astrocytes. Rat and mouse MHC antigen class II was only detected on leukocytes and activated microglia. We suggest that host macrophages and activated host and xenograft microglial cells act in situ as immunostimulatory cells on T-helper cells, and that increased levels of donor MHC antigen class I may further enhance the killer activity exerted by host T-cytotoxic cells.

Acid Anhydride Hydrolases↗
PubMed1991

Attenuated renal excretory response to atrial natriuretic peptide in congestive heart failure in man.

The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0 micrograms/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P less than 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1991

Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna.

The circadian variation of plasma atrial natriuretic peptide (ANP) in relation to urinary excretion of sodium (UNa) and potassium (UK) as well as clearance of creatinine (Ccrea) was assessed in 15 juvenile patients with enuresis nocturna and compared with 11 age-, sex-, and weight-matched normal subjects. Normal juveniles showed a highly significant diurnal variation (p less than 0.001) of plasma ANP with diurnal peak levels at midnight (0000 hours) and minimum levels at 0400 hours. Enuretic patients showed a similar diurnal rhythmicity with normal levels during day and night. In normals both UNa and UK showed significant diurnal rhythmicity with a marked reduction from daytime to night-time. Although the total diurnal excretions of UNa and UK were similar to normals, patients with enuresis showed abnormal diurnal variation in both UNa (p less than 0.05) and UK (p less than 0.01). The abnormal circadian rhythm of UNa and UK in enuretics seemed to be caused by abnormal tubular handling as similar abnormalities were found in the fractional excretions and as the circadian variation of Ccrea was normal. Especially during the first hours of sleep (2200 hours to 0000 hours), the patients showed polyuria (230 +/- 138 ml vs 116 +/- 58 ml, p less than 0.01), natriuresis (20.9 +/- 16.3 mmol l-1 vs 10.7 +/- 6.8 mmol l-1, p less than 0.01), and kaliuresis (7.3 +/- 6.3 mmol l-1 vs 3.7 +/- 2.3 mmol l-1, p less than 0.05), despite normal levels of plasma ANP. In conclusion, the study describes the diurnal variation of plasma ANP in relation to urinary excretion of sodium and potassium in a juvenile normal population. Patients with nocturnal enuresis show abnormal diurnal rhythmicity in the urinary excretion of sodium and potassium that is not correlated to the plasma levels of ANP.

Adolescent↗
PubMed1991

Enhanced urinary excretion of albumin and beta 2 microglobulin in essential hypertension induced by atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) was given as an intravenous bolus injection (2.0 micrograms kg-1) to 12 essential hypertensive patients (EH) and 10 normotensive control subjects (C) in order to study the effect of ANP on urinary excretion of albumin and beta 2-microglobulin, and on glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF). After the ANP injection, urinary excretion of albumin increased significantly (p less than 0.01) in EH from 7.3 micrograms min to 125 micrograms min (medians) and in C from 2.9 micrograms min-1 to 8.1 micrograms min-1 (p less than 0.05). Urinary excretion of beta 2-microglobulin increased in EH from 70 ng min-1 to 1022 ng min-1 (p less than 0.01) and in C from 118 ng min-1 to 170 ng min-1 (p less than 0.01). The increase in urinary excretion of both albumin (p less than 0.01) and B2-microglobulin (p less than 0.01) was significantly more pronounced in EH than in C. GFR and RPF were almost unchanged in both groups. FF rose to the same degree in the two groups. The increase in fractional excretion of sodium and in urine volume after ANP was enhanced in EH. It is concluded that ANP in pharmacological doses increased urinary excretion of albumin and beta 2-microglobulin to a considerably larger extent in essential hypertensive patients than in normotensive control subjects.

Adult↗
PubMed1991

Effect of fish protein supplementation on aminoacid profile and nutritional status in haemodialysis patients.

Plasma concentrations of aminoacids, albumin, prealbumin, transferrin, C3 and C4 complement, and anthropometric measurements were determined before and after oral administration of a new preparation of fish protein in 19 haemodialysis patients participating in a randomised, double-blind, placebo-controlled crossover study lasting 6 months. Furthermore, plasma concentrations of aminoacids were measured in 24 control subjects. Before fish protein dietary supplementation, serine, threonine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, and lysine were lower than in control subjects. Serine, histidine, valine, tyrosine, methionine, isoleucine, leucine, and lysine increased after treatment, and phenylalanine tended to increase. The ratios of essential: non-essential aminoacids and alanine:branched-chain aminoacids (BCAA) became normal, whereas valine: lycine and serine:glycine increased significantly and tyrosine:phenylalanine was unchanged. Plasma protein concentrations were unchanged after treatment. Serum transferrin, triceps and subscapular skinfolds, and bodyweight index were slightly reduced in the patients, whereas arm muscle circumference was normal. Bodyweight, weight index, and arm muscle circumference increased after active treatment. In conclusion, the increase in body weight and the return to normal of the plasma aminoacid profile and aminoacid ratios seem to indicate that the treatment with this new fish protein preparation may have beneficial effects on some of the nutrition-related abnormalities in haemodialysis patients.

Adult↗
PubMed1991

Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients.

Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods. Thus, CaCO3 treatment seems to slow down loss of bone mineral content, and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover.

Adult↗
PubMed1991

Effect of frusemide on atrial natriuretic peptide, guanosine cyclic monophosphate, angiotensin II, aldosterone, vasopressin, prostaglandin E2 and blood volume in the nephrotic syndrome.

Blood volume, plasma concentrations of atrial natriuretic peptide, guanosine cyclic monophosphate (cGMP), angiotensin II, aldosterone and arginine vasopressin, and urinary excretion rate of prostaglandin E2, cGMP, sodium, and water were determined before and after intravenous administration of frusemide 0.75 mg/kg body-weight in nine patients with the nephrotic syndrome and 15 control subjects. The decrease in blood volume and the increase in urinary sodium and water excretion after fusemide were significantly reduced in the nephrotic patients compared with the controls. Atrial natriuretic peptide was reduced after frusemide both in patients (6.2 to 4.9 pmol/l, medians, P less than 0.05) and controls (5.9 to 4.8 pmol/l, P less than 0.01), but the nadir was delayed in the patients, and cGMP in plasma and urine was reduced only in the controls. The angiotensin II increase was delayed in the patients and aldosterone increased only in the controls. Basal urinary excretion of prostaglandin E2 was less in the nephrotic patients than in the controls (P less than 0.05), but after frusemide the prostaglandin E2 excretion rate increased in the patients (0.25 to 0.62 pmol/min, P less than 0.05), but not in the controls (0.46 to 0.39 pmol/min). In conclusion, reduced water and sodium excretion after frusemide in the nephrotic syndrome is accompanied by a diminished reduction of blood volume, a delayed decrease in atrial natriuretic peptide, and a blunted increase in angiotensin II and aldosterone compared with healthy subjects. Sodium excretion after frusemide may be more dependent on PGE2 production in nephrotic patients than in healthy subjects.

Adult↗
PubMed1991

Effect of two regimens of intravenous amino acid infusion on renal haemodynamics, renal tubular function and sodium and water homeostatic hormones in healthy humans.

The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon.

Adult↗
PubMed1991

Abnormal glomerular and tubular response to intravenous frusemide in patients with chronic glomerulonephritis.

Fourteen normotensive patients with chronic glomerulonephritis and well-preserved renal function and thirteen healthy control subjects were studied. Glomerular filtration rate (GFR), proximal and distal absolute and fractional tubular reabsorption (PAR, PFR, DARNa, DFRNa), evaluated by the lithium clearance technique, were determined before and in four 30-60-min periods after intravenous injection of frusemide 0.5 mg/kg body weight (Study 1) and 1.0 mg/kg body weight (Study 2). Plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressine (AVP) were measured before, and 60 and 180 min after frusemide. GFR decreased and UNa and FENa increased significantly in patients and controls after frusemide in both studies, but in study 2 GFR decreased significantly more in patients than in controls, and UNa and FENa increased significantly less above baseline in patients compared to controls. PAR, PFR, DARNa, and DFRNa were reduced in patients and controls in both studies. In study 2 the reduction in PAR was significantly (P less than 0.05) less pronounced in patients (23%) than in controls (43%), whereas DARNa was reduced significantly more (P less than 0.05) in patients (36%) than in controls (21%). The efficiency of frusemide with regard to renal sodium excretion was significantly reduced in patients compared to controls in both studies. Angiotensin II and aldosterone increased, ANP decreased, and AVP was unchanged in patients and controls in both studies. It is concluded that in comparison to control subjects, patients with chronic glomerulonephritis and well-preserved GFR respond to frusemide with an exaggerated reduction in GFR, a lesser decrease in absolute proximal tubular reabsorption, and a larger reduction in absolute distal tubular reabsorption. Thus, primary glomerular disease with well-preserved glomerular function may be accompanied by a distinctly disturbed tubular function.

Adult↗