Does magnesium play a role in the hypokalemia of Bartter's syndrome?

A patient with Bartter's syndrome manifested hypomagnesemia in addition to hypokalemia. Under conditions of maximal free water production, he had a fractional distal solute reabsorption of 0.65, a value consistent with a renal defect in sodium chloride reabsorption in the thick ascending limb of the loop of Henle. This is also the site of 65% to 70% of urinary magnesium reabsorption. With magnesium supplementation and amiloride, the urinary potassium decreased and the serum potassium increased. Atrial natriuretic peptide concentrations in the plasma were low. Evaluation of family members showed five of nine offspring had hypokalemia with no disorder in the parents, an apparent autosomal recessive mode of inheritance. This is a US government work. There are no restrictions on its use.

Renal tubular reabsorption of chloride in Bartter's syndrome and other conditions with hypokalemia.

Fractional distal chloride reabsorption was measured in 8 patients with Bartter's syndrome, 8 patients with comparable degrees of hypokalemia of different etiologies and 7 normal subjects during maximal diuresis induced by an intravenous infusion of 5% dextrose in water. A low fractional distal chloride reabsorption (0.55 +/- 0.01) was found only in patients with Bartter's syndrome, whose serum potassium concentrations ranged between 1.2 and 3.1 mEq/l. Non-Bartter's syndrome hypokalemic patients had serum potassium concentrations between 2.4 and 3.2 mEq/l (p NS when compared to patients with Bartter's syndrome) but their fractional distal chloride reabsorption was 0.88 +/- 0.33, significantly higher (p less than 0.001) than that of patients with Bartter's syndrome. Normokalemic control subjects had a fractional distal chloride reabsorption of 0.86 +/- 0.01, higher than patients with Bartter's syndrome (p less than 0.001) but not significantly different from patients with hypokalemia. These results suggest that there is no effect of serum potassium concentration on fractional distal reabsorption of chloride in man. Hypokalemia of a moderate to severe degree is not accompanied by obligatory renal chloride loss except in Bartter's syndrome. Chloruresis is a specific feature of Bartter's syndrome rather than an effect of hypokalemia.

The effects of oral furosemide on the response of urinary excretion of cyclic adenosine monophosphate and phosphate to parathyroid extract in normal subjects.

We studied the effects of oral furosemide, 80 mg/day for 7 days, on the response of urinary excretion of phosphate and cyclic AMP to exogenous parathyroid extract (PTE) in 6 normal subjects. All 6 subjects had marked increases in urinary calcium and a significant increase in urinary cyclic AMP from the control to the furosemide periods: this suggests that furosemide-induced hypercalciuria produced elevated parathyroid activity. After treatment with furosemide, the response of urinary cyclic AMP and phosphate to PTE was blunted. During the subsequent calcium infusion (4 mg/kg), urinary cyclic AMP was suppressed to subnormal values, and the response to PTE returned to normal. The evidence suggests that furosemide may blunt the response to PTE, perhaps as a result of the elevated parathyroid activity produced by furosemide-induced hypercalciuria and lowering of plasma-ionized calcium. This blunting effect of furosemide on the response of urinary phosphate and cyclic AMP to PTE should be considered in the evaluation of parathyroid function in patients taking furosemide.

The effect of vasopressin in water-loaded hypokalemic patients is prostaglandin-independent.

Potassium-depleted subjects regularly excrete dilute urine with a high free-water clearance which cannot be suppressed either by solute loading or by water deprivation. In man, as in the dog and rat, potassium depletion impairs the ability of the kidney to achieve maximal urinary solute concentration and vasopressin is unsuccessful in overcoming this defect. In man and in the dog, potassium depletion induces a rise in urinary prostaglandin E2, an effect which can be reversed with indomethacin, a cyclo-oxygenase inhibitor. To evaluate the role of prostaglandins on the renal action of vasopressin in hypokalemia, six subjects with hypokalemia of various etiologies were studied in a control, drug-free condition and again after 3 to 6 days of indomethacin (100 mg/day). Renal clearance studies to measure the maximal free-water excretion in response to an intravenous water load (10 ml/min) and to a superimposed infusion of arginine vasopressin (40 mU/hr) were performed. The results in six patients are as follows: maximal free-water clearance (control) 8.03 +/- 0.8 ml/min (mean +/- S.E.), with the addition of vasopressin, .14 +/- 0.8; after 3 to 6 days of indomethacin, 8.55 +/- 1.33; with vasopressin 0.91 +/- 1.23 ml/min. There was no statistically significant difference between the maximal free water clearance with or without indomethacin. Vasopressin exerted an equally great response in both conditions and prostaglandins did not appear to play a role in free-water formation.

Nephropathologic characteristics of a woman with Bartter's syndrome after prolonged treatment with spironolactone.

A study was made of two renal biopsy specimens obtained from a 22-year-old woman with Bartter's syndrome, the first to substantiate the diagnosis, the second 2 years later after the treatment with spironolactone. The first renal biopsy revealed remarkable hyperplasia and hypertrophy of the juxtaglomerular apparatus. The numerous proliferating cells were characterized by abundant lysosomal granules and dilated endoplasmic reticulum. The macula densa revealed slight proliferation, with narrow intercellular space. The ultrastructural picture of the second biopsy specimen showed increased lipofuscin-like granules in the juxtaglomerular cells, with epitheloid cells of the macula densa showing degeneration and irregular dilatation of the intercellular spaces. However, the light microscopic finding was compatible with that of the first. These findings suggest that the treatment was inadequate although clinical features or biochemical laboratory data were improved.

Schedule shifts, life quality and quantity--modeled by murine blood pressure elevation and arthropod life span.

During the span from 50 to 100 days and beyond, the male stroke-prone Okamoto rat develops systolic blood pressure measures in excess of 200 mm Hg. In the course of developing such a marked elevation in systolic blood pressure mean, this intermittently handled male Okamoto rat exhibits a statistically significant circadian rhythm with large amplitude. This amplitude may represent, at least in part, a response to intermittent handling; it is several times larger than the amplitude for spontaneously mesor-hypertensive (but not stroke-prone) female animals of the same age.

Chronobiology of blood pressure.

Blood pressure in normal and hypertensive subjects shows circadian variability with the minima during the hours of sleep. The factors influencing blood pressure show circadian variability, in particular, plasma and urinary aldosterone, plasma deoxycorticosterone and urinary sodium (factors implicated in cardiac output), angiotensin II as measured by plasma renin activity, plasma and urinary epinephrine and norepinephrine, and plasma and urinary prostaglandins of the E series (factors implicated in peripheral resistance). Direct causal relationships have not been established. The treatment of hypertensive subjects in relation to the circadian variability is reviewed.

The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension.

Nineteen patients with hypertension in whom all known causes of blood pressure elevation had been ruled out were classified as "salt-sensitive" or "nonsalt-sensitive" from the changes in blood pressure with changes in sodium intake from 9 meq to 249 meq/day. With the diet containing 249 meq sodium per day, there were no statistically significant differences in plasma sodium, potassium, chloride, aldosterone, cortisol or renin activity, or in urinary potassium, aldosterone or 17-hydroxycorticosteroids between the two groups. The "salt-sensitive" patients retained more sodium on the high-sodium diet than did the patients who were not sensitive to salt ("nonsalt-sensitive"); accordingly, sodium induced more weight gain in the salt-sensitive patients.

Chronobiology in the diagnosis and treatment of mesor-hypertension.

An elevation of systolic and diastolic bloodpressure to values regarded as abnormal ones on the basis of conventional criteria was recognized by self-measurement. For both systolic and diastolic blood pressure, the overall means adjusted for rhythms, the so-called mesors, also were elevated in the light of their response to treatment: these mesors were found to be lowered with statistical significance when values during treatment were compared by an objective test with values measured before treatment. Individualized rhythmometry quantitatively characterizes a predictalbe portion of the variability in human blood pressure and tests for the statistical significance of changes in blood pressure as a function of the treatment and also as a function of the circadian timing of such treatment. The case report thus illustrates an individualized chronotherapy of systolic and diastolic mesor-hypertension, diagnosed retrospectively from the tested effect of hydrochlorothiazide. In the case reported, and perhaps routinely, computer-analyzed self-measurements can serve 1) to prescribe the right kind and amount with the right timing, for a given therapy, and 2) for diagnosis and prevention as well (Meyer et al.; Halberg et al.).

Increase in renin release after sionaortic denervation and cervical vagotomy.

The role of the vagi in the control of renin secretion was investigated in dogs maintained on a high-salt diet. Renal perfusion pressure was maintained relatively constant by the manipulation of a suprarenal aortic snare. Mean arterial blood pressure (MAP), plasma renin activity (PRA), and packed cell volume (PCV) increased after sinoaortic denervation and cervical vagotomy. Cooling of cervical vagi to 3-5 degrees C had the same effect as vagotomy. There was no change in MAP, PRA, and PCV in sham-operated animals. Propranolol prevented the increase in PRA following sinoaortic denervation and vagotomy, but not that in MAP or PCV. In splenectomized dogs, PCV still showed increases after sinoaortic denervation and vagotomy. It is suggested that the removal of sinoaortic and/or vagal inhibitory effects on the vasomotor center causes increases in sympathetic discharge to the adrenal medulla and the peripheral vessels, and that this in turn leads to the increase in MAP. The increase in sympathetic discharge to the adrenal medulla and the kidney causes the increases in PRA.

Ewing's sarcoma as a cause of the syndrome of inappropriate secretion of antidiuretic hormone.

A patient with Ewing's sarcoma presented with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (1). Plasma values for vasopressin were found to be over four times the normal values expected for the plasma osmolality. At postmortem examination, the arginine vasopressin concentration in the tumor tissue was ten times that of the plasma. These data suggest that Ewing's sarcoma may cause SIADH.