The development of a radioimmunoassay for arginine vasopressin.

The development of a sensitive and specific radioimmunoassay for vasopressin is described. Antibodies were successfully produced following the coupling of synthetic arginine vasopressin with bovine serum albumin carried out with carbodiimide. In order to standardize the assay, the labelled hormone has to be separated twice using a DEAE-Sephadex-A-25 column and thin layer chromatography with cellulose plates. A further condition to obtain a reproducible standard curve is the use of a pure arginine vasopressin checked by cellulose chromatography. Most of the vasopressin batches available do not fulfil this requirement of purity. With the method described, vasopressin can be determined in unextracted human urine. The lower limit of detection is 2 pg/ml. Normal values are in the range of 67.5 +/- 34.3 ng/24 h (kappa +/- SD, n =45). No significant difference of AVP excretion was found between men and women. The usefulness of the assay is demonstrated in patients with hypothalamic or pituitary disorders.

[Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)]. / Spezifische und unspezifische Wirkungen von beta-Sympatholytika am Menschen

The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity.

Correlation between increased dopamine-beta-hydroxylase activity and catecholamine concentration in plasma: determination of acute changes in sympathetic activity in man.

In 11 healthy untrained volunteers the increase in plasma dopamine-beta-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130+/-3% and 820+/-71%, respectively; the adrenaline concentration in plasma increased only to 150+/-19% (p less than 0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net ""overflow'' from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20-22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.