Hormonal control of sodium content in human milk.

The possible role of prolactin (PRL) and aldosterone (Aldo) in regulation of Na content of human milk was investigated. Simultaneous determinations of Na and K in milk, PRL and Aldo in maternal plasma and milk were performed on postpartum days 2, 4 and 6, in samples from 15 mothers giving birth at term and from 8 mothers giving preterm birth. Na concentration and Na/K ratio in milk, Aldo concentration in milk and maternal plasma decreased significantly with advancing lactation. In preterm plasma and milk PRL concentration remained unchanged, whereas in term plasma PRL decreased, milk PRL increased significantly by the 6th day post partum. After preterm delivery milk Na and K levels were significantly higher, maternal plasma and milk Aldo slightly lower than after delivery at term. Daily Aldo and PRL excretion into the milk markedly increased during lactation irrespective of the length of gestation and showed a significant negative correlation with milk Na level and Na/K ratio. It is suggested that the increasing rate of Aldo and PRL excretion into the milk may be of importance in the regulation of Na concentration in human milk.

Activity of the renin-angiotensin-aldosterone system in full-term newborn infants during the first week of life.

A study was performed in 7 healthy full-term newborn infants with mean birth weight of 3130 g (range, 2650-2850 g) and a mean gestational age of 38.8 weeks (range, 37-41 weeks) to investigate the postnatal changes of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) in relation to electrolyte balance. PRA, PA and UAE fell significantly from their initially high values of 28.36 +/- 3.6 ng/ml/hr 1.5 +/- 3 ng/ml and 7.1 +/- 1.9 microgram/day on the first day to 6.84 +/- 2.9 ng/ml/hr (p less than 0.01), 0.71 +/- 0.1 ng/ml (p less than 0.01) and 5.5 +/- 1.6 microgram/day (p less than 0.05), respectively, on the 5th day. No significant correlation was found between either PRA and PA or PA and UAE. PRA and UAE showed a significant negative correlation with dietary sodium intake, the other parameters of sodium and potassium homeostasis, however, had no apparent influence on the activity of RAAS. The initial high level and the rapid postnatal decline in RAAS activity has been attributed to perinatal stress imposed by labour and delivery and not to the changes in sodium or potassium balance in the early days of life.

Furosemide-induced alterations in the electrolyte status, the function of renin-angiotensin-aldosterone system, and the urinary excretion of prostaglandins in newborn infants.

To assess the responsiveness of the renin-angiotensin-aldosterone system of the neonate to acute furosemide stimulation and the role of renal prostaglandins in mediating the response of the renin-angiotensin-aldosterone system, this study was carried out to determine simultaneously plasma renin activity, plasma aldosterone concentration, urinary aldosterone, prostaglandin E, and prostaglandin F2 alpha excretion along with determination of plasma electrolyte concentration and urinary electrolyte excretion. Measurements were made on 19 newborn infants with mean birth weight and gestational age of 3009 g (range, 2700 to 4150 g) and 38.7 wk (range, 36 to 41 wk) at the age of 4 to 7 days before and after IM administration of furosemide in a dose of 1 mg/kg. It was demonstrated that in response to furosemide, urine volume (P less than 0.001), urinary sodium (P less than 0.001), potassium (P less than 0.05), and chloride (P less than 0.001) excretion increased significantly. Furosemide administration also resulted in a significant increase from 4.41 +/- 2.00 to 9.70 +/- 2.32 ng/ml/hr (P less than 0.02) in plasma renin activity, from 1.17 +/- 0.22 to 1.68 +/- 0.36 ng/ml (P less than 0.025) in plasma aldosterone, from 0.93 +/- 0.16 to 1.53 +/- 0.35 microgram/12 hr (P less than 0.025) in urinary aldosterone, from 17.53 +/- 3.37 to 23.73 +/- 3.16 ng/12 hr (P less than 0.025) in prostaglandin E, and from 16.48 +/- 4.12 to 26.27 +/- 4.12 ng/12 hr (P less than 0.05) in prostaglandin F2 alpha. It is concluded that the renin-angiotensin-aldosterone system of the neonate responds to acute furosemide challenge in spite of its high baseline activity, and its response may be mediated by increased renal prostaglandin production.

Sodium, potassium and aldosterone content of human milk during the first postnatal week.

In an attempt to obtain information about the hormonal control of the sodium content of human milk, simultaneous determinations were performed of the Na, K and aldosterone concentrations in milk samples collected from 6 mothers on the 2nd, 4th and 6th days after delivery. Na concentration (p less than 0.01), Na/K ratio (p less than 0.01) and aldosterone concentration (p less than 0.01) decreased significantly with advancing lactation. The rate of daily aldosterone excretion, however, rose considerably from 4.8 +/- 0.9 ng/day (mean +/- SE) on the 2nd to 12.2 +/- 1.6 ng/day on the 6th day post partum (p less than 0.01). A significant negative correlation was found between daily aldosterone excretion and Na concentration (p less than 0.05), as well as between aldosterone excretion and Na/K ratio (p less than 0.05) in human milk during the first week after delivery. It is suggested that the rate of aldosterone excretion may be of importance in the regulation of the Na concentration in human milk.

Function of the renin-angiotensin-aldosterone system in relation to electrolyte balance in the small-for-date neonate.

To assess the influences of intrauterine growth retardation on the electrolyte status and the activity of renin-angiotensin-aldosterone system of newborn infants, sodium and potassium balance, as well as plasma renin activity, plasma aldosterone concentration and urinary aldosterone excretion were determined simultaneously in a group of healthy growth retarded and healthy normally grown neonates. It was observed that intake, urinary excretion and retention rate of sodium and potassium as well as the plasma sodium and potassium levels were essentially the same in the two groups. Similarly, no significant difference was found in plasma renin activity, plasma aldosterone level and urinary aldosterone excretion between the neonates whose birth weight was small or appropriate for gestational age. It is concluded that intrauterine growth retardation has no significant influence on the electrolyte status and the activity of the renin--angiotensin--aldosterone system, suggesting that in the regulation of these functions gestational factors are mainly involved.

HLA antigens in chronic active hepatitis.

Seventy-five patients (28 HBsAg-positive and 28 HBsAg-negative) with chronic active hepatitis (CAH) were studied for HLA antigens. In the whole material, the HLA antigens were distributed as in the controls, with the only exception of the HLA-A9 antigen, the frequency of which, as compared with the controls, was moderately increased (37.4% against 22.7%). It was mainly the HBsAg-negative group which showed a significant increase in the frequency of the HLA-A9 antigen (42.9%). In the HBsAg-negative group, as compared with the HBsAg-positive group, where the frequency of HLA-A2 was 53.2%--and as compared with the controls, too--it was relatively low 29.3%. The frequency of HLA-A1 and HLA-B8 was not increased in any type of chronic active hepatitis. HLA-B8 was less frequent in the HBsAg-positive than in the HBsAg-negative group (10.6% against 21.4%).

Postnatal development of renin-angiotensin-aldosterone system, RAAS, in relation to electrolyte balance in premature infants.

In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160-1850 g, and mean gestational age of 31 weeks, range: 30-32 weeks, were selected for the study. Due to the increased urinary Na loss, negative Na balance developed in the first 2 weeks followed positive balance thereafter. PRA, PA, and UAE increased tremendously from the initially high values of 18.2 +/- 4.1 ng/ml/hr, 1.7 +/- 0.5 ng/ml, and 2.6 +/- 0.4 microgram/day, mean and SEM, to their maximum of 78.6 +/- 18.1 ng/ml/hr, p less than 0.01, 6.8 +/- 3.7 ng/ml, p less than 0.05, and 26.4 +/- 2.9 microgram/dayp less than 0.01, in the 3rd week, respectively. Later on, gradual declines occurred, however, PRA, PA, and UAE remained highly elevated even at the 6th week with values of 45.5 +/- 15 ng/ml/hr, 1.6 +/- 0.5 ng/ml, and 14.5 +/- 1.4 microgram/day, respectively. It is suggested that late hyponatremia of premature infants is due to tubular unresponsiveness to aldosterone and not to inadequate response of RAAS to stimulation.

The possible role of prostaglandins in the hyperfunction of the renin-angiotensin-aldosterone system in the newborn.

Plasma renin activity and plasma aldosterone concentration were measured by radioimmunoassay in eight newborn infants born vaginally to mothers on indomethacin treatment. Measurements were made in venous cord blood at birth and on the sixth day of life. The results were compared to those obtained in eight healthy control newborn infants of similar gestational age and birth weight. Maternal treatment with indomethacin was associated with a decrease of plasma renin activity (mean +/- SD) from 16.71 +/- 2.76 ng/ml/hour in the control group to 9.60 +/- 3.84 ng/ml/hour in the treated group. Plasma aldosterone concentration was lower in the cord blood of the treated group and a similar trend was demonstrated in the sixth day samples. It is suggested that the increased endogenous prostaglandin production during labour may be one of the factors responsible for the development of hyperactivity of renin-angiotensin-aldosterone system in the newborn.

Study of the renin-angiotensin system in essential hypertension.

320 patients with essential hypertension divided into three groups (minor, medium and major severty) were studied against 50 normal controls. Plasma renin activity (PRA) was estimated in case of normal and low Na intake, furthermore, of low Na intake in association with administration of chlorothiazide, in the recumbent position as well as at the end of 4-hr walk. The hypertensive group of medium severity (Group II) revealed a significant decrease in PRA, compared with the controls and with the hypertensive group of minor severity (Group I), in each period of observation. A significant increase of PRA in response to insulin hypoglycaemia was demonstrable in all three groups and in the controls, but the increase was of significantly lesser degree in Group II than either in the controls or in Group I. The plasma catecholamine concentrations were found lower in Group II than in the controls and in Group I. An elevation of the plasma catecholamine levels was demonstrable in response to insulin hypeglycaemia, but it was of lesser degree in Group II than a Group I and in the controls. The poor responsiveness of the RAS in Group II is attributed to an inadequate adrenergic activity and to an increased mean arterial pressure in that group, but the higher age of patients and longer duration of hypertensive disease, both characteristic of the group of medium severity, may also effect the renin-angiotensin system.

Relationship between maturity, electrolyte balance and the function of the renin-angiotensin-aldosterone system in newborn infants.

Simultaneous measurement of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) was made using the RIA method along with determination of Na and K balance in 1-week-old neonates with gestational age of 30-41 weeks (mean 35.9 weeks) and birth weight of 1,160-4,670 g (mean 2,680 g). It was demonstrated that PRA decreased from the value of 36.3 +/- 6.3 ng/ml/h (mean +/- SE) to a level of 10.2 +/- 2.1 ng/ml/h (p less than 0.001), PA did not change and UAE increased from 3.3 +/- 0.8 to 7.8 +/- 1.4 microgram/day (p less than 0.01) as the gestational age advanced from 30-32 to 39-41 weeks. There was no correlation between either PRA and PA and UAE. PRA showed a significant positive correlation with urinary Na excretion (p less than 0.001) and plasma K concentration (p less than 0.05), but it was negatively related to Na balance (p less than 0.001). Significant negative correlations were found between UAE and urinary Na excretion (p less than 0.05), urinary Na/K ratio (p less than 0.01 (and plasma K concentration (p less than 0.05); however, UAE positively correlated with Na balance (p less than 0.01). It is concluded that, in response to renal salt wasting and to the subsequent negative salt balance, premature infants can augment their PRA above values found for full-term infants. Their adrenals, however, failed to respond adequately to this stimulation.

Nepresol in the treatment of hypertension of major severity.

Fifty patients with arterial hypertension of various causes were treated with a combination consisting of Nepresol, a beta-adrenergic receptor-blocking agent and a diuretic. Duration of treatment ranged between 3 months and 5 years. A significant reduction of blood pressure was attained in all of the cases, with a return of the values to the normal range in a high proportion of the patients. The renal function did not deteriorate during therapy, but owing to potassium loss regular potassium replacement was required in the majority of the cases. Allergic reactions appeared in two cases. Neither SLE nor rheumatoid arthritis was encountered. Positive ANF reaction and a significant elevation of the Rose-Waaler titre were demonstrated in a number of cases. The benefits as well as the hazards of the therapeutic use of hydrazine derivatives are pointed out.

The effect of pindolol on plasma renin activity in patients with essential hypertension.

Twenty-two patients with essential hypertension were treated for 3 months with pindolol, and blood pressure and plasma renin activity were measured at rest and after stimulation (upright posture stimulation and insulin induced hypoglycaemia stimulation). Beta-receptor blockade produced a significant decrease in systolic and diastolic blood pressure. After treatment with pindolol the plasma renin activity was significantly lower. Under conditions of renin stimulation such as orthostasis and insulin produced hypoglycaemia, plasma renin activity was significantly lower in treated patients. There was no correlation between the fall of plasma renin activity and the decrease of blood pressure. Renin suppression is probably only one of the factors involved in the reduction in the blood pressure in these patients.

The effects of EDTA and EGTA on renin secretion.

1 The effects of the disodium salt of ethylenediamine tetra-acetate (EDTA) and 1, 2, bis, 2 aminoethoxyethane-NNN'N'-tetra-acetic acid (EGTA) on renin secretion and vascular resistance were studied in the isolated perfused kidney of the rat. 2 Both substances produced a significant increase of renin release 3 In the absence of calcium and magnesium, EDTA still increased rein release and there was now a considerable increase of perfusion pressure. 4 The rise of pressure but not the rise of renin was inhibited by the removal of potassium from the perfusate when EDTA was administered in the absence of calcium. 5 Propranolol and phenoxybenzamine had no effect on the vasoconstrictor action of EDTA. 6 EGTA was less effective as a renin releaser than EDTA until magnesium was removed from the perfusate. Furter, it had only a small effect on perfusion pressure in contrast to EDTA.