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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

24-hour serum concentration profile of cortisol in patients with Cushing's disease.

To evaluate whether or not patients with Cushing's disease can be differentiated from those with obesity by the determination of 24-hour integrated serum concentrations of cortisol we studied healthy, nonobese males (n = 5), as well as patients with marked obesity (n = 5) and with Cushing's disease (n = 7) in whom diagnosis was established biochemically and subsequently confirmed by surgery. Serum cortisol concentrations in samples collected continuously by a portable blood withdrawal pump during 24 hours (08:00-08:00h) were 6.6 +/- 1.7 micrograms/dl and 8.4 +/- 1.5 micrograms/dl in nonobese and obese individuals, respectively. Patients with Cushing's disease presented a mean cortisol concentration of 21.4 +/- 6.4 micrograms/dl (p vs normal: less than 0.005; vs obesity: less than 0.005). Collecting consecutive samples in 4-h periods the decline of serum cortisol from peak to nadir values was 73 +/- 10% and 57 +/- 23% in normal males and obese subjects, respectively, while a decline of only 22 +/- 8% was seen in patients with Cushing's disease. Three of the patients with Cushing's disease exhibited a circadian rhythm of cortisol albeit on an elevated level. These results may reflect variable stages of autonomy in pituitary ACTH-production and hence a possible criteria for differentation of hypothalamic and pituitary forms of Cushing's disease. In regard to differential diagnosis between Cushing's disease and obesity the 24-hour cortisol profile obtained by multiple sampling did not provide additional information to that obtained by a single sample pooled for 24 hours, which was diagnostic in each case.

Adrenocorticotropic Hormone↗

Effect of human atrial natriuretic peptide on 1-deamino-D-Arg8-vasopressin-induced antidiuresis in man.

The interaction of exogenous synthetic human atrial natriuretic peptide (hANP), given in iv bolus doses of 100, 200, and 400 micrograms, and of various bolus-primed infusion of 1-deamino-D-Arg8-vasopressin (dDAVP), a nonpressor analog of antidiuretic hormone, were investigated in six normal men. A marked dose-dependent rise in plasma hANP concentrations occurred after the administration of hANP. The antidiuretic effect of dDAVP (P less than 0.01) was partially but not completely reversed by the concomitant administration of hANP (P less than 0.01). hANP-induced natriuresis was similar in the presence and absence of dDAVP-induced antidiuresis. While these results do not prove that hANP-dependent natriuresis and diuresis are independent phenomena, it is of clinical interest that natriuresis without diuresis can be induced by the simultaneous administration of hANP and dDAVP.

Adult↗

[Detection of primary aldosteronism using the captopril test].

In order to evaluate whether changes in the plasma concentration of aldosterone (PA) following the administration of captopril, an inhibitor of angiotensin-converting enzyme, will establish the diagnosis of primary aldosteronism we have used this test in 9 healthy subjects and in 22 patients with various forms of hypertension, including 5 patients with primary aldosteronism due to idiopathic adrenal hyperplasia (n = 4) or aldosterone-producing adenoma (n = 1). The response of PA to captopril (25 mg orally) was investigated on an outpatient basis, following a rest period of 120 minutes in the supine position. In healthy subjects PA decreased from a mean basal value of 11.5 +/- 5.9 ng/dl to less than 6.4 ng/dl (4.9 +/- 1.4 ng/dl [p less than 0.01]). Similarly, captopril induced a fall in PA concentration to less than 6.4 ng/dl in patients with essential hypertension, with renal artery stenosis or with an afunctional kidney. Post-captopril concentrations of plasma aldosterone were about twice the normal level in 3 of 4 patients with idiopathic adrenal hyperplasia and about four-fold raised above normal in the patient with an aldosterone-producing adenoma. In spite of a false-negative result in one patient with idiopathic adrenal hyperplasia, the administration of captopril appears to be of use in recognizing patients with primary aldosteronism on an outpatient basis.

Adenoma↗

[Human atrial natriuretic peptide: a secretory product of the heart and its significance for physiology and clinical practice].

This review deals with the physiological and clinical importance of human atrial natriuretic peptide (hANP). This peptide, which is produced by the myocardial cells of the right atrium, induces a diuretic and natriuretic response and has an inhibitory effect on aldosterone secretion. Recent elucidation of the peptide's structure represents the latest achievement in the search for an endogenous, natriuretic and hypotensive substance and has resulted in the publication of much, partly only preliminary data of its role within the homeostatic control of body sodium and water, as well as in various pathological disorders. The extensive literature is reviewed.

Aldosterone↗

Prolonged administration of human atrial natriuretic peptide in healthy men: evanescent effect on diuresis in spite of simultaneous infusion of norepinephrine.

In healthy, sodium and fluid replete men (n = 6) a transient increase in diuresis is seen during the prolonged infusion of human atrial natriuretic peptide (hANP: 50 micrograms h-1 for 6 h). In order to evaluate whether this evanescent diuretic effect of hANP is due to the peptide's hypotensive action, the latter was compensated for by the concomitant infusion of norepinephrine (NE: 50 ng kg-1 min-1). The decrease in hANP-induced diuresis towards the end of the 6-h infusion was not prevented by the additional infusion of norepinephrine, which also failed to influence hANP-stimulated natriuresis. Plasma concentrations of hANP, which were continuously elevated to about double of basal concentrations during the infusion of hANP, were not affected by exogenous norepinephrine. These data demonstrate that the transient character of hANP-induced diuresis cannot be offset by counterbalancing the peptide's hypotensive effect.

Adult↗

A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol.

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.

Adult↗