M. Damkjaer Nielsen

Male pseudohermaphroditism due to 5α-reductase deficiency in a Swedish family

Three sibs with an inherited form of male pseudohermaphroditism are described. They were all born with ambiguous external genitalia but no diagnosis of a possible enzyme defect was made during childhood. First seen at the ages of 16, 14 and 10 years respectively, they were investigated in order to establish the pathogenetic nature of the disorder. Serum concentrations of testosterone and dihydrotestosterone before and after stimulation with human chorionic gonadotropin suggested 5α-reductase deficiency. Measurement of steroid metabolites in urine confirmed this diagnosis. It is essential to recognize this condition in order to decide the sex of rearing of the children.

The renin-angiotensin-aldosterone system in normal 85-year-old people.

Active and total plasma renin concentration, as well as plasma angiotensin II, aldosterone and renin substrate concentrations were measured in venous blood samples from 17 normal 85-year-old people at rest. No discernible sex-related differences were seen. Active plasma renin and plasma aldosterone concentrations were significantly lower in the old people compared to a group of normal 40-year-old people. Plasma angiotensin II concentration showed no decrease with increasing age. Active plasma renin concentration constituted approximately 20% of total plasma renin concentration, with a significant correlation between the two renin moieties. The values for plasma renin substrate concentration are similar to those reported for younger age groups. The lack of standardization of methods severely hampers inter-laboratory comparisons of both active plasma renin and total plasma renin concentrations.

The effect of angiotensin II blockade by saralasin (1-Sar-8-Sla-angiotensin II) in normal man

SummaryThe effects of the angiotensin II analogue saralasin were investigated in 6 normal individuals. Blood pressure, plasma renin (PRC), plasma aldosterone (PAC) and plasma saralasin were measured before and during infusion of saralasin (0.54–5.4 nmol/kg/min) with the subjects supine. Plasma angiotensin II concentration (PA II) was measured before the infusion. In the sodium replete state, PA II averaged 11 pmol/1 (range 5 to 17). Saralasin infusion produced an increase in mean arterial pressure (MAP) and PAC, and a slight fall in PRC, which is consistent with an angiotensin II-like effect or a so-called agonistic effect. After sodium depletion, induced by hydrochlorothiazide 50–100 mg/day for 5 days, PA II was high −91 pmol/l on average (range 41 to 217). Angiotensin II blockade produced a fall in MAP in the supine position. The agonistic effect of saralasin on adrenal receptors during sodium depletion was less pronounced or absent. PRC increased sharply during the infusion. Infusion of saralasin at the rate of 5.4 nmol/kg/min produced a plasma saralasin concentration of about 220 nmol/l, i. e. in molar terms the plasma concentration of the analogue was 2000 to 10000 times higher than that of the endogenous octapeptide. The relationship between changes in MAP and basal PA II prior to infusion showed that saralasin exhibited a shift from agonistic to antagonistic properties on vascular receptors when pre-infusion PA II changed from approximately 20 to 40 pmol/l. A shift from agonistic to antagonistic effect on aldosterone secretion was not consistently seen. It is concluded that angiotensin II does not have a decisive role in the maintenance of normal blood pressure during normal sodium balance. However, after sodium depletion the renin-angiotensin system contributes to blood pressure control, even in the supine position. In addition to its antagonistic properties, saralasin possesses a weak agonistic effect on vascular, as well as on renal and adrenal receptors. This has to be taken into consideration when saralasin infusion is used to define “angiotensin II dependency” in patients with hypertension.

Haemodynamic and humoral effects of lower body negative pressure in normal, sodium-replete man during angiotensin-converting enzyme inhibition with captopril.

The significance of the renin-angiotensin system (RAS) for circulatory homeostasis during gravitational stress (10 min of lower body negative pressure, LBNP, at -40 mmHg) was investigated in eight men on liberal sodium intake. The function of RAS was inhibited by a single oral dose of 100 mg captopril, an angiotensin-converting enzyme inhibitor. Plasma concentrations of renin and angiotensin I were normal before and increased after captopril and during LBNP. Plasma concentration of angiotensin II was normal before captopril, increased during LBNP, and fell to low values after captopril. Systolic blood pressure decreased more during LBNP after captopril than in the control situation. In three cases, the LBNP experiment after captopril had to be interrupted due to marked hypotension. Heart rate and plasma concentration of adrenaline increased above pre-captopril levels. In six subjects, plasma concentration of noradrenaline increased more during LBNP after captopril, less in two subjects, whereas the arginine vasopressin concentration increased more after captopril in all five subjects where measurements were available. The results demonstrate that RAS participates in blood pressure homeostasis also in sodium-replete, normal man. The enhanced increases in heart rate and plasma catecholamines after captopril do not suggest that sympathetic reflex activity during gravitational stress is blunted after captopril, in contrast to the evidence from animal experiments.