Effect of low dose infusion of atrial natriuretic peptide on renal function in man.

1. The effects of the infusion of a low dose (2 pmol min-1 kg-1 for 3 h) of human atrial natriuretic peptide (hANP) were studied in seven healthy volunteers undergoing a water diuresis. Lithium clearance was used to monitor proximal tubular function. 2. hANP increased urine flow rate, sodium, calcium and magnesium excretion without significant changes in potassium and phosphate excretion, heart rate or blood pressure. 3. hANP caused a small change in fractional lithium clearance, and larger changes in distal nephron handling of sodium and water. 4. Plasma renin activity tended to decrease during the infusion of hANP, while plasma aldosterone concentration decreased during and increased after stopping the infusion of hANP. 5. The data suggest that hANP inhibits the reabsorption of sodium and water by an action on distal segments of the nephron and perhaps the proximal tubule. Inhibition of renin and aldosterone secretion may contribute to the natriuresis.

Effect of a meal containing protein on lithium clearance and plasma immunoreactive atrial natriuretic peptide in man.

1. The effect of meals with a high and low protein content and of the fasting state on renal function and plasma atrial natriuretic peptide was studied in water-loaded normal volunteers. 2. Creatinine clearance increased after the high protein meal, but did not change after the low protein meal or while fasting. Observations of similar increases in urine sodium and potassium excretion and a transient decrease in urine flow after both meals suggest that the protein content of the meal is not an important contributory factor in these responses to feeding. 3. Absolute delivery of sodium and water out of the proximal tubules (assessed by the lithium clearance method) was higher after both meals than while fasting; fractional lithium clearance was higher after the low protein meal than the high protein meal and while fasting. Absolute reabsorption from proximal tubules was increased after only the high protein meal. 4. A transient decrease in the fraction of water delivered to distal nephron segments that appeared in the urine (fractional distal water excretion) was observed after both meals. Fractional distal sodium excretion and absolute distal sodium and water reabsorption increased after both meals. 5. Since plasma atrial natriuretic peptide either decreased (high protein meal) or remained unchanged (low protein meal and fasting), it is unlikely that this hormone is involved in the hyperfiltration after the high protein meal and the natriuresis after both high and low protein meals.

Effect of dietary sodium chloride and posture on plasma immunoreactive atrial natriuretic peptide concentrations in man.

The effect of changes of dietary sodium chloride intake and posture on plasma atrial natriuretic peptide concentration and renal function was studied in 11 normal human volunteers. Plasma atrial natriuretic peptide concentration was higher in the upright posture on a high than it was on a medium or low salt diet. On the medium and high but not on the low salt diet the concentration increased significantly on adoption of the supine posture. Creatinine, sodium, lithium and fractional lithium clearances, fractional distal sodium excretion and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, were significantly higher on the high than on the low salt diet. The medium salt intake gave intermediate values. Heart rate while upright was significantly higher on the low than on either the medium or the high salt diets. Systolic blood pressure was unaffected by salt intake. Diastolic blood pressure in the supine position was significantly higher on the low than on the medium or high salt diets. Both plasma noradrenaline concentrations and plasma renin activity were significantly higher on the low than on the high salt diet. Values on the medium salt intake were intermediate. Plasma concentrations of both hormones were higher in the upright than in the supine posture on all three salt intakes. The data are consistent with the hypothesis that atrial natriuretic peptide contributes to the cardiovascular and renal adjustments to changes in dietary sodium chloride, and the possible role of the peptide is discussed.

Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man.

The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30-60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.

Bartter's syndrome--observations on the pathophysiology.

The pathophysiology of Bartter's syndrome affecting seven adults has been investigated. (1) Saralasin infusion caused a fall in blood pressure in all patients, suggesting that angiotensin was contributing to the maintenance of blood pressure. (2) Following a water load, urinary chloride concentrations and osmolality were both low. No positive evidence for a defect in chloride reabsorption in the ascending limb of the loop of Henle was obtained. (3) The effect of high and low dietary sodium on plasma sodium, potassium, chloride, magnesium, renin activity, aldosterone, 6-keto-PGF1a, thromboxane B2, urinary kallikrein, platelet function and erythrocyte membrane cation transport were studied. A variety of responses was observed. Sodium restriction increased (or sodium loading decreased), plasma renin activity, aldosterone, 6-keto-PGF1a, urinary kallikrein and the platelet aggregation abnormality in some, but not all, individuals. (4) Treatment with indomethacin was undertaken in all patients and studied in detail in one patient. There was weight gain, increase in plasma sodium and potassium, decrease in capillary pH, positive sodium and potassium balance, and decrease in plasma renin activity, 6-keto-PGF1a, thromboxane B2 and urinary kallikrein. Hypomagnesaemia and excessive urinary magnesium loss persisted unchanged. (5) A variety of abnormalities of erythrocyte membrane cation transport was found and these persisted during high- and low-sodium, and high-potassium intakes; and during treatment with indomethacin, despite correction of intracellular sodium and potassium concentrations. Bartter's syndrome is associated with an abnormality of erythrocyte membrane sodium and potassium transport. Many of the other metabolic abnormalities may be the consequence of potassium and sodium depletion.

Effect of acetylcholine stimulation on calcium and sodium uptake by the isolated rat pancreas.

1. The role of Ca2+ and Na+ ions in 'stimulus-secretion' coupling in the isolated uncinate pancreas of 4-week-old rats has been examined using radioisotope tracer techniques. The amount of 45Ca2+ and 22Na+ (mumole/g wet wt.) taken up by unstimulated glands was compared to that of glands in which amylase release was stimulated by ACh(10(-5) M) at various incubation times. 2. The amount of 45Ca taken up by the glands within 60 min of incubation was not found to be increased by the presence of ACh(10(-5) M). In fact, during short incubation periods the 45Ca uptake was significantly less in the stimulated glands than the unstimulated glands. 3. Presence of ACh(10(-5) M) did cause a significant initial increase in 22Na uptake lasting up to 20 min from onset of stimulation. 4. These results indicate that the rise in intracellular Ca2+ concentration which is suggested by an increase in 45Ca efflux during the action of pancreatic secretagogues, is not a consequence of increased 45Ca uptake by the pancreas; but they indicate that an initial action of ACh could be to elicit an increase in Na+ influx and that Na+ ions are likely to be involved in the action of ACh on pancreatic acinar cells.

Altered membrane sodium transport and the presence of a plasma ouabain-like inhibitory factor in acute myeloid leukaemia.

1. Sodium transport studies were performed in erythrocytes from normal subjects and from patients with acute myeloid leukaemia. Sodium influx and efflux rates were increased in erythrocytes from leukaemic patients. 2. The ouabain-sensitive component of sodium efflux was increased in leukaemic erythrocytes. 3. The high sodium efflux from leukaemic erythrocytes was decreased when the incubation media contained leukaemic plasma, suggesting the presence of an ouabain-like factor in the plasma. Paired experiments failed to show the presence of a similar factor in normal plasma. 4. Leukaemic erythrocytes showed a significantly greater ouabain uptake than the normal cells. 5. The results are discussed in relation to the wide-spread electrolyte disturbances in acute myeloid leukaemia.