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Biomedical subjects

H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 145 records · Page 8Linked to original sources
PubMed1991

Suramin and the human adrenocortex: results of experimental and clinical studies.

Suramin, a sulfonated drug, has been used successfully in the treatment of inoperable adrenocortical cancer. This study was undertaken to investigate the effects of suramin on the basal and the adrenocorticotropin-stimulated cortisol and pregnenolone secretion and on the proliferation of primary monolayer cultures of normal human adrenocortical cells. Suramin decreases basal and adrenocorticotropin-stimulated cortisol secretion in a dose-dependent manner (p less than 0.05 from 0.3 mmol/L upward). At a suramin concentration of 3 mmol/L cortisol, secretion was inhibited by 70% +/- 4% in adrenocorticotropin-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was inhibited by suramin at concentrations from 0.3 mmol/L upward, maximal suppression (71% +/- 6%; p less than 0.05) being observed at a concentration of 10 mmol/L. Neither down-regulation of cortisol secretion nor inhibition of adrenocortical cell proliferation was caused by toxicity of the compound, as could be shown by adrenocorticotropin-restimulating cortisol secretion in suramin-treated cells. The results indicate that suramin exerts an inhibitory influence on the cortisol secretion and the proliferation of normal human adrenocortical cells and may be useful in treating adrenocortical cancer.

Adrenal Cortex↗
PubMed1991

Contribution of leg vascular tissues to the overall metabolic clearance of human atrial natriuretic factor (hANF) in man.

From experimental studies it has been suggested that considerable peripheral clearance of human atrial natriuretic factor (hANF) might occur. In healthy men (n = 7) the peripheral fractional extraction of hANF was about 35% under basal conditions resulting in hANF-uptake across the leg vascular bed of 2.1 +/- 2.4 pMol/min and regional leg clearance rate of 102.6 +/- 88.2 ml/min, which is approximately 2.5% of the total metabolic clearance rate. During a primed constant i.v. infusion of hANF (bolus 100 micrograms; infusion 100 micrograms/h, t = 1h) arterial and venous plasma concentrations of hANF increased about 10-fold (p less than 0.05), however, estimated leg blood flow as well as leg fractional extraction, leg uptake and clearance rates of hANF did not significantly change as compared to baseline. Total metabolic clearance rates and apparent production rates of hANF were 4.05 +/- 1.93 l/min and 84.1 +/- 29.9 pMol/min, respectively. We conclude that in healthy man the leg vascular bed does not play a major regulatory role in the metabolism of exogenously infused hANF. However, our results suggest that the peripheral vasculature is, to a certain extent, involved in the metabolic clearance of endogenous hANF and thus, contributes to the peptide's overall disposal.

Adult↗
PubMed1990

Renal disposal of human atrial natriuretic peptide in man.

In healthy men (n = 7) the renal fractional extraction of human atrial natriuretic factor (hANP) as determined by the renal venous catheter technique was approximately 50% both under basal conditions and during the administration of exogenous hANP. When arterial and venous plasma concentrations of hANP were maintained about tenfold above basal concentrations by a bolus- (100 micrograms) primed intravenous (IV) infusion (100 micrograms/h for 1 hour) of hANP, renal uptake of hANP increased from, basal, 11.2 +/- 6.7 pmol/min to 126.5 +/- 64.8 pmol/min (P less than .05), while estimated renal plasma flow (ERPF) decreased by about 25% (P less than .05). Total metabolic clearance rates (MCRs) of hANP, renal clearance rates, and production rates of hANP were 3.89 +/- 1.21 L/min, 0.42 +/- 0.18 L/min, and 76.1 +/- 52.7 pmol/min, respectively. In healthy men, one kidney accounts for about 10% of total hANP clearance.

Adult↗
PubMed1990

Formation of androstanediol from 13C-labeled testosterone in humans.

The determination of urinary 5 alpha-androstane-3 alpha,17 beta-diol (3a-Diol) by gas chromatography/mass spectometry during and after the infusion of stable-labeled testosterone (T) represents an alternative to the use of radioactive label for turnover studies in vivo. Using this methodology to assess the urinary excretion rates of T and 3a-Diol in healthy men (n = 6) and women (n = 5) during and after the intravenous infusion (t = 4 hours) of 20 mg (men) or 5 mg (women) [13C]testosterone, the cumulative renal excretion of 13C-labeled T was found to be 15.6 +/- 9.6 micrograms/24 hours (men) and 1.1 +/- 1.6 micrograms/24 hours (women), equivalent to 0.08% +/- 0.05% and 0.02% +/- 0.03% of the infused amount of 13C-T, respectively. The cumulative excretion of 13C-3a-Diol was 67.7 +/- 19.9 micrograms/24 hours (men) and 10.0 +/- 6.0 micrograms/24 hours (women), equivalent to 0.3 +/- 0.1% and 0.2 +/- 0.1% of the infused dose of 13C-labeled testosterone, respectively.

Adult↗
PubMed1990

Permissive action of glucocorticoid substitution therapy on the effects of atrial natriuretic peptide (hANP) in patients with adrenocortical insufficiency.

To study the potential impact of glucocorticoids on the effects of human atrial natriuretic peptide (hANP) in man, the diuretic and natriuretic response to intravenous bolus doses of hANP (50 and 100 micrograms) was studied in seven male patients with deficient endogenous glucocorticoid synthesis, both during withdrawal of glucocorticoid therapy and during subsequent substitution with dexamethasone. Plasma concentrations of ACTH, though markedly suppressed by dexamethasone as compared to the unsubstituted state were not influenced by exogenous hANP either during deprival or substitution of glucocorticoids. Basal plasma concentrations of hANP were 10.3 +/- 8.4 pmol/l and 19.3 +/- 11.1 pmol/l during glucocorticoid withdrawal and following substitution with dexamethasone, respectively. When substituted with glucocorticoids, patients responded to hANP (100 micrograms) with an increase (p less than 0.025) in diuresis and sodium excretion, whereas no changes in diuresis and sodium excretion were seen following intravenous hANP during glucocorticoid withdrawal. These results suggest that glucocorticoids may have a permissive effect on hANP-mediated natriuresis and diuresis.

Adrenal Glands↗
PubMed1990

Action of endogenous atrial natriuretic peptide in calves with experimental acute central venous congestion and low cardiac output.

STUDY OBJECTIVE: The aim of the study was to investigate plasma concentrations of atrial natriuretic peptide, aldosterone, and renin during experimentally induced acute central venous congestion. DESIGN: Two experimental calf models were used: (1) right heart failure due to pulmonary artery obstruction; (2) inferior vena cava syndrome produced by inferior vena caval obstruction. Hormonal responses and haemodynamic variables were measured over 6 h. SUBJECTS: Experiments were performed on three female "Schwarzbund" calves, age 3 months, weight 92 +/- 8 kg. MEASUREMENTS AND MAIN RESULTS: In the pulmonary artery obstructed group there was an increase of plasma aldosterone from 6.5(SEM 1.6) to 22.1(3.2) ng.dl-1 (p less than 0.05), of renin from 0.7(0.1) to 2.5(0.3) Goldblatt units x 10(-4).ml-1 (p less than 0.05), and of atrial natriuretic peptide from 22.1(4.5) to 141.4(27.8) pmol.litre-1 (p less than 0.05). During inferior vena caval obstruction, aldosterone increased from 2.4(0.4) to 20.9(2.0) ng.dl-1 (p less than 0.05), and renin increased from 0.4(0.05) to 2.0(0.20) Goldblatt units x 10(-4).ml-1 (p less than 0.05). In this experiment, atrial natriuretic peptide remained unchanged. Cardiac output decreased in both groups. There was significant fluid and electrolyte retention during both experiments, with urine volume decreasing from 87.7(11.6) to 35.0(1.2) ml-h-1 in experiment (1), and from 185(14) to 95.7(8.6) ml.h-1 in experiment (2). CONCLUSIONS: The study suggests (1) that in an experimental acute state of reduced cardiac output due to pulmonary artery stenosis with constantly increased right heart pressures, raised endogenous atrial natriuretic peptide failed to induce diuresis and natriuresis; (2) that in acute right heart failure, renin and aldosterone secretion could not be suppressed by raised atrial natriuretic peptide concentrations; and (3) atrial natriuretic peptide secretion seemed to be exhausted after 6 h continuous atrial distension.

Acute Disease↗
PubMed1990

Plasma concentrations of endothelin in man: arterio-venous differences and release during venous stasis.

Endothelin-1 is a recently described endothelium-derived vasoconstricting peptide. Plasma concentrations of immunoreactive (IR-) endothelin were investigated in six healthy young men applying a radioimmunoassay after extraction of endothelin from plasma. In venous plasma a mean concentration of 1.3 +/- 0.4 pmol l-1 was found, whereas the mean concentration in arterial plasma was 0.9 +/- 0.4 pmol l-1 (P less than 0.005). During venous stasis for 10 min the mean plasma concentration of IR-endothelin increased about twofold, from basal 1.1 +/- 0.3 pmol l-1 to 2.1 +/- 0.3 pmol l-1 (P less than 0.01). This manoeuvre may prove helpful to investigate the control of endothelin in vivo under a variety of pathological conditions.

Adult↗
PubMed1990

Effect of endothelin-1 in man.

The effect of an intravenous infusion of human endothelin-1 on blood pressure and plasma concentrations of endothelin-1, potassium, sodium, renin, aldosterone, and atrial natriuretic factor was investigated in six healthy, sodium-loaded men. During the peptide's exogenous application (1.0, 2.5, and 5.0 ng/kg.min), its plasma concentrations rose from a basal value of 1.2 +/- 0.3 to 3.2 +/- 1.9, 9.9 +/- 7.6, and 56.5 +/- 50.3 pmol/l (p less than 0.01), respectively, and mean blood pressure rose from a basal value of 87.1 +/- 7.3 to 92.6 +/- 8.2 mm Hg (p less than 0.01). A rise in serum concentrations of potassium (from 4.0 +/- 0.3 to 4.6 +/- 0.2 mmol/l; p less than 0.005) and a concomitant fall in serum concentrations of sodium (from 142.7 +/- 1.0 to 139.5 +/- 2.3 mmol/l; p less than 0.05) was seen in each subject. Plasma concentrations of renin, aldosterone, and atrial natriuretic factor did not change during the infusion of endothelin-1. Thus, in the doses used, endothelin-1 induces a rise in blood pressure and serum potassium concentrations.

Adult↗
PubMed1990

Metabolism of cortisol in anorexia nervosa.

In patients with anorexia nervosa 24-h mean plasma concentration of cortisol were 0.44 +/- 0.09 mumol/l (normal less than 0.28 mumol/l). Following stimulation by ACTH (1-24) urinary excretion rates of cortisol were stimulated from 0.22 +/- 0.08 to 4.85 +/- 2.78 mumol/24 h. Similarly, plasma concentrations of the glucocorticoid metabolite, tetrahydrocortisone, increased from 23.3 +/- 9.0 to 47.3 +/- 30.2 nmol/l; urinary excretion rates of tetrahydrocortisone increased from 3.61 +/- 0.90 to 8.40 +/- 1.72 mumol/24 h. The relative share of the sulphate, glucuronide and free fractions of tetrahydrocortisone in the patients' urine did not indicate any defect in metabolization of this steroid metabolite. Excretion rates of the four glucocorticoid tetrahydro-metabolites, tetrahydrocortisone, allotetrahydrocortisone, tetrahydrocortisol, and allo-tetrahydrocortisol, expressed as percent of total steroid excretion, were similar in patients with anorexia and in healthy women under basal conditions (24 +/- 6 vs 23 +/- 6%) and during stimulation by ACTH (1-24) (36 +/- 10 vs 45 +/- 6%). The share of the two androgen metabolites, androsterone and etiocholanolone, was 24 +/- 5% of total steroid excretion (basal; healthy women: 27 +/- 8%) and 13 +/- 2% (ACTH stimulation; healthy women: 12 +/- 4%) in patients with anorexia nervosa. Thus, analysis of urinary steroid excretion rates did not indicate a shift in adrenocortical function. The results confirmed enhanced secretion of cortisol in patients with anorexia nervosa under basal conditions and during/following stimulation by ACTH. The ACTH-induced increase in the concentrations of the tetrahydro-glucocorticoid metabolites in urine was less pronounced than that of cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

The diuretic and natriuretic action of human atrial natriuretic peptide in humans: lack of effect of exogenous insulin.

The interaction of exogenous, synthetic human atrial natriuretic peptide [(hANP) (ANF 99-126)] and of exogenous insulin was investigated in six healthy men and in seven type I diabetic patients using the euglycemic clamp technique. A primed-continuous (1.0 mU/kg x min) infusion of biosynthetic human insulin was administered to acutely raise and maintain plasma insulin concentrations at approximately 75 to 100 microU/mL during four hours while plasma glucose concentrations were maintained constant at the fasting level by a variable infusion of glucose. In healthy men a decrease in natriuresis (P less than .01) was seen during a euglycemic clamp study without exogenous hANP. No changes in diuresis and natriuresis were seen during a control experiment without exogenous insulin and glucose. Both in healthy men and in the type I diabetics sequential IV bolus doses of hANP of 100, 200, and 400 micrograms induced an increase in urine flow (P less than .01) and in natriuresis (P less than .01). In healthy men these effects were comparable to those achieved by hANP in the absence of induced hyperinsulinemia. It is concluded that the antinatriuretic action of insulin is of no major relevance in counteracting the pharmacologic action of hANP in healthy men. The effects of pharmacologic doses of hANP on diuresis and natriuresis in patients with type I diabetes mellitus is comparable to that in healthy men.

Adult↗
PubMed1989

Effect of cardiac tamponade on plasma concentrations of atrial natriuretic peptide (ANP) in calves.

To study the effect of cardiac tamponade on plasma concentrations of atrial natriuretic peptide (ANP) female calves received an infusion of 450 ml of 0.9% saline into the pericardial space. This was accompanied by a parallel rise in both, right atrial pressure (from 4.5 +/- 2.6 mm Hg to 14.1 +/- 3.8 mm Hg (p less than 0.01] and in intrapericardial pressure (from 0.4 +/- 2.0 mm Hg to 12.9 +/- 3.9 mm Hg (p less than 0.01] and a fall in cardiac output from 11.4 +/- 1.9 l/min to 8.5 +/- 2.4 l/min (p less than 0.01). Plasma concentrations of ANP remained unchanged in 7 of 9 experiments. During these seven experiments plasma concentrations of renin and aldosterone increased from 0.65 +/- 0.27 X 10 E-4 GU/ml to 1.04 +/- 0.43 X 10 E-4 GU/ml (p less than 0.01) and from 2.7 +/- 0.9 ng/dl to 11.4 +/- 6.1 ng/dl (p less than 0.01), respectively. On two occasions, which were characterized by an excessive fall in cardiac output (to less than 40% of initial values) cardiac tamponade was followed by an extensive rise in the plasma concentrations of ANP, renin and aldosterone. These results indicate that an increase in intra-atrial pressure per se is not the decisive factor in the control of ANP secretion. Since atrial transmural pressure does not change during cardiac tamponade ANP concentrations are, as a rule, unaltered by that condition. An increase in plasma ANP is seen only during preshock hemodynamic conditions possibly due to a reduced intra-atrial volume.

Aldosterone↗
PubMed1988

Influence of indomethacin on PGE2 in rabbit aqueous humor after YAG laser photodisruption of the iris.

In an experimental study with rabbits, the influence of indomethacin on the postoperative PGE2 level in the aqueous humor was investigated, following YAG laser traumatization of the iris. Indomethacin is a drug with an inhibitory effect on the synthesis of prostaglandins. Using albino rabbits, the right eye was treated with indomethacin eye drops three times daily for 3 days. On the 4th day, high-energy YAG laser was applied to the iris of both eyes (Q-switched Nd: YAG Laser, Model Cilco Lasertek PV 135; ten photodisruptive lesions, with 50 mJ to the midperiphery of the iris). Subsequently, the rabbits were subdivided into three groups. In group 1 the aqueous humor was removed from both eyes 12 h postoperatively; in group 2 the aqueous humor was tapped 36 h after the intervention; for group 3, it was 60 h afterwards. The results from 15 rabbits were evaluated. Local indomethacin treatment was continued until tapping of the aqueous humor. As a control, another group was used with 3 rabbits without treatment. Twelve hours after YAG laser treatment there was still a clearly significant difference in the PGE2 concentrations between the eyes that had received indomethacin and the untreated eyes; 36 h postoperatively, the difference was no longer statistically significant, and after 60 h the PGE2 concentrations of the treated and untreated eyes were the same.

Animals↗
PubMed1988

Estimation by gas chromatography-mass spectrometry with selected ion monitoring of urinary excretion rates of 3 alpha-androstanediol during/after i.v. administration of 13C-labelled testosterone in man.

To study in vivo the conversion of testosterone (T) into its metabolites, dihydro-testosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta diol (3 alpha-Diol) the urinary excretion rates of these steroids were determined by mass spectrometry in 6 healthy men during/after the i.v. infusion (t = 4 h) of 20 mg [13C]testosterone. In addition, plasma concentrations of T, DHT and 3 alpha-Diol were determined by radioimmunoassay. During steady state conditions at the end of the 4-h infusion of [13C]T the increase in the plasma concentrations of T from, basal, 405 +/- 140 ng/dl to 4205 +/- 804 ng/dl was paralleled by an increase in the plasma concentrations of DHT to 106.4 +/- 62.5 ng/dl) (basal: 30.8 +/- 21.8 ng/dl), and of 3 alpha-Diol to 32.2 +/- 12.5 ng/dl (basal: 12.5 +/- 13.9 ng/dl). Plasma concentrations of T, DHT and 3 alpha-Diol then returned to basal concentrations within 24 hours. Using mass-spectrometry we found a cumulative renal excretion of 13C-labelled T of 15.6 +/- 9.6 micrograms/24 h, equivalent to 0.08 +/- 0.05% of the infused amount (20 mg) of [13C]T. Whereas urinary excretion of [13C]DHT was below the level of detection by mass-spectrometry the cumulative excretion of [13C]3 alpha-Diol was 67.7 +/- 19.9 micrograms/24 hours which is equivalent to 0.3 +/- 0.1% of the infused dose of 13C-labelled testosterone. These data suggest that the determination of urinary 3 alpha-Diol by mass-spectrometry during/after the infusion of stable-labelled testosterone represents an alternative to the use of radioactive label for turnover studies.

Adult↗
PubMed1988

Splanchnic disposal of human atrial natriuretic peptide in humans.

In healthy men (n = 6), the splanchnic fractional extraction of human atrial natriuretic peptide (hANP), as determined by the hepatic venous catheter technique, was 75% under basal conditions resulting in a splanchnic uptake of hANP of 8.5 +/- 5.0 pmol/min. In spite of a drop (P less than .05) in splanchnic fractional extraction to about 50%, splanchnic uptake of hANP rose to 56 to 99 pmol/min (P less than .01) when pharmacologic plasma concentrations of hANP were induced during a bolus (100 micrograms)-primed intravenous (IV) infusion (100 micrograms/h; time, one hour) of hANP. This was accompanied by a fall in estimated hepatic blood flow (P less than .05), in pulmonary arterial pressure (P less than .01), and, in each individual, in systemic BP. Total metabolic clearance rates, splanchnic clearance rates, and production rates of hANP were 4.5 +/- 2.2 L/min, 0.4 +/- 0.1 L/min, and 46.1 +/- 20.1 pmol/min, respectively. Thus, in healthy men, the splanchnic area accounts for approximately 10% of total hANP clearance.

Adult↗