A circaoctohoran rhythm of urine epinephrine excretion in man.
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Activity Cycles↗
Biomedical subjects
F C Bartter
Publications and source records attributed to F C Bartter.
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.
Calcium↗
Effects of oral furosemide and salt loading on parathyroid function in normal subjects. Physiological basis for renal hypercalciuria.
With oral furosemide administration and salt loading, urinary calcium was significantly increased in 8 normal subjects, accompanied by parallel natriuresis. In spite of the excessive calcium loss in the urine, total and ionized serum calcium remained unchanged. All subjects had significant increases in nephrogenous cyclic AMP, suggesting that parathyroid activity is elevated in subjects with furosemide-induced hypercalciuria. With furosemide, fecal calcium was significantly decreased, and resultantly, there was no significant change in the cumulative calcium balance. It is suggested that urinary calcium loss with furosemide is compensated for by secondary hyperparathyroidism via increased intestinal calcium absorption in order to maintain serum calcium at a normal level. The experimental model thus mimics the condition of the renal type of idiopathic hypercalciuria.
Calcium↗
A sibship with hypokalemic alkalosis and renal proximal tubulopathy.
A new syndrome, characterized by hypokalemic alkalosis, hyperreninemia, aldosterone, high urinary prostaglandin E2 excretion, normal BP, and resistance of BP to angiotensin II is described in three of four siblings. Histologic examination of tissue obtained by biopsy from the kidneys showed an intense staining of the proximal tubular cells, as well as an extreme hypertrophy of the proximal tubular basement membranes, features that previously have not been observed. On electron microscopic examination, the characteristic changes of the tubular cells consisted of very dense cytoplasm, compact mitochondria, and pyknotic nuclei. In contrast to Bartter's syndrome, the juxtaglomerular apparatus were of normal appearance. Glomerular filtration rate and renal plasma flow were within normal limits. Fractional distal delivery of proximal tubular solute and fractional chloride reabsorption in the thick ascending limb of the loop of Henle were normal. The findings of a genetic linkage between the syndrome and the major histocompatibility system suggests that this familial tubulopathy is an inherited disorder.
Aldosterone↗
Lack of evidence for a role for prostaglandins in the mediation of impaired urinary concentrating ability in Bartter's syndrome.
Imparied urinary concentrating ability in Bartter's syndrome may result in part from overproduction of prostaglandins and from the defect in chloride reabsorption by the loop of Henle, or both. To assess the role of prostaglandins, concentration of the urine before and after treatment with prostaglandin inhibitors was studied in 3 patients with this syndrome, taking a constant metabolic diet. Maximal urinary osmolality was determined after overnight fluid deprivation and during infusion of Pitressin. The studies were repeated after 4 days of treatment with the prostaglandin inhibitors, indomethacin and ibuprofen. The maximal urinary osmolality was 694 +/- 39 and 717 +/- 78 mosm/kg, and solute clearance was 1.3 +/- 0.3 and 1.2 +/- 0.5 ml/min for the control and treatment periods, respectively. Prostaglandin inhibitors failed to increase the maximal urinary osmolality or solute clearance. The data thus suggest that factors other than prostaglandin overproduction cause the impairment in urinary concentration in Bartter's syndrome. The defective chloride transport with a loss of interstitial hyperosmolality may be one such factor.
Adolescent↗
Effect of inhibition of prostaglandin synthesis on urinary free dopamine excretion in women.
1. The effect of inhibition of prostaglandin synthesis on urinary excretion of free dopamine, a catecholamine thought to act as a renal natriuretic hormone, was examined in six normal women. 2. The volunteer subjects were treated with indomethacin (2 mg day-1 kg-1) for 7 days. This regimen produced an immediate and significant but transient decrease in urinary sodium excretion, averaging about 80 mmol over a period of 3 days. 3. Urinary dopamine excretion during the control period was not different from that during the entire period of indomethacin treatment. 4. It is concluded that indomethacin does not affect urinary dopamine excretion. The change in intrarenal nervous release of dopamine in response to the sodium retention induced by indomethacin may have been too small to make a significant contribution to total urinary dopamine excretion.
Adult↗
The response of plasma immunoreactive adrenocorticotropin, beta-endorphin/beta-lipotropin, gamma-lipotropin and cortisol to experimentally induced pain in normal subjects.
1. We examined the effect of ischaemic pain and sustained isometric muscle contraction on plasma immunoreactive gamma-lipotropin (gamma LPH), beta-endorphin/beta-lipotropin (beta END/beta LPH) and corticotropin (ACTH), which are all synthesized from a common precursor (pro-opiocortin), and plasma cortisol in 10 normal subjects. 2. Experimental pain was produced by inflation to 250 mmHg of a sphygmomanometer cuff, placed above the elbow of the 'dominant' arm, after which the subject squeezed a hand dynamometer, loaded to 12 kg, 20 times at 2 s intervals. Blood was drawn before, after 5 and 10 min of pain, and 30 min after release of the cuff. In a control session, the subjects were asked to squeeze the handgrip alone for 5 min at 30% of their maximum strength, a procedure which elevates the blood pressure without causing pain. 3. One subject had unexplained high (30--71 pmol/l) baseline peptide concentrations. Baseline values for the nine other subjects were: ACTH, 7.3 +/- 1.9 pmol/l (mean +/- SEM); gamma LPH, 18.6 +/- 1.0 pmol/l; beta END/beta LPH, 10.0 +/- 1.1 pmol/l; cortisol, 599 +/- 55 nmol/l. Neither procedure significantly increased the plasma concentration of ACTH or any other peptide, whereas plasma cortisol was significantly increased at both 5 min and 10 min. Plasma ACTH was positively correlated with plasma gamma LPH (r = 0.701; P less than 0.001), beta END/beta LPH (r = 0.970; P less than 0.001) and plasma cortisol (r = 0.758; P less than 0.05). 4. The present study demonstrates that, in normal man, plasma endorphins do not change with experimental ischaemic pain. The rise in plasma cortisol without concomitant rise in ACTH is not explained, but suggests the action of some other agent at the level of the adrenal cortex.
Adrenocorticotropic Hormone↗
Effect of bradykinin on renal function in dogs treated with indomethacin or propranolol.
The effect of bradykinin (BK) on renal function was examined in anesthetized dogs with or without treatment with either indomethacin or propranolol. Renal arterial infusion of BK (3 micrograms/min) in control dogs produced a sustained increase in urine flow rate (V), sodium excretion (UNaV), potassium excretion (UKV), and renal plasma flow (RPF) without a consistent change in glomerular filtration rate (GFR) or renin secretion rate (RSR). This increase in salt and water excretion and in RPF could not be blocked with indomethacin (5 mg/kg, followed by 2.1-3.2 mg/kg/h, i.v.). UNaV was 20.8 +/- 7.4 and 123.3 +/- 22.3 muEq/min (mean +/- SEM values) before and after 140 min of infusion of BK (p less than 0.005), respectively. Beta-receptor blockade with propranolol (5 mg/kg, followed by 2.8-3.4 mg/kg/h, i.v.) did not prevent the BK-induced rise in salt and water excretion, or in RPF. UNaV was 26.0 +/- 9.7 and 96.4 +/- 21.5 muEq/min before and after 140 min of infusion of BK (p less than 0.005), respectively. The data suggest that the effects of BK on renal handling of salt and water and on RPF are not mediated by either prostaglandins or beta receptors.
Animals↗
The role of prostaglandins in diabetes insipidus produced by desoxycorticosterone in the dog.
To determine the role of renal prostaglandins (PGs) in the renal response to desoxycorticosterone acetate (DOCA), dogs were studied on a constant diet in which sodium intake was restricted (2.5 meq/day) or high (115 meq/day). On the restricted sodium intake, DOCA (25 mg/day im for 6 days) did not affect urinary volume, sodium, potassium, PGE2, or PGF2 alpha. On the high sodium intake, DOCA produced sodium retention for 1 day and a sustained increase in urinary potassium with a fall in serum potassium to 3.1 meq/liter. Urine volume increased from 574 +/- 50 to 1726 +/- 177 ml/day (P less than 0.001) with a fall in urinary osmolality from 1545 +/- 122 to 495 +/- 55 mosmol/ liter (P less than 0.001) as serum sodium increased from 149.0 +/- 1.0 to 152.5 +/- 0.3 meq/liter (P less than 0.025) by the sixth day of DOCA. Urinary PGE2 and PGF2 alpha were unchanged during the first 2 days of DOCA, then increased progressively from control values of 261 +/- 60 and 1143 +/- 144 ng/day ng/day, respectively, to 730 +/- 62 (P less than 0.005) and 3013 +/- 479 ng/day (P less than 0.01), respectively. Potassium repletion during continued DOCA treatment restored urinary volume, osmolality, PGE2 and PGF2 alpha, and serum sodium to control values. Treatment with indomethacin during DOCA-induced hypokalemia, polyuria, hypernatremia, and increased urinary PG, restored urinary PGs to control values, and corrected the polyuria and hypernatremia without a change in serum potassium. Thus, DOCA produced potassium depletion, polyuria, increased urinary PGs, and hypernatremia in dogs on a high sodium intake but not in those on a restricted sodium intake. As polyuria and hypernatremia were corrected either by potassium repletion, which corrected the supranormal renal synthesis of PGs, or by indomethacin, which inhibited their synthesis, renal water loss was presumably the result of an increase in renal PG synthesis, probably stimulated by potassium depletion.
Animals↗
Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids.
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Aldosterone↗
Bartter's syndrome.
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Acidosis, Renal Tubular↗
Vasopressin and blood pressure.
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Animals↗
Essential hypertension: central and peripheral norepinephrine.
The concentration of norepinephrine in cerebrospinal fluid from patients with essential hypertension is higher than that from healthy normal volunteers, but the concentrations of norepinephrine in plasma from these groups are similar. This finding indicates that central nervous system noradrenergic hyperactivity occurs in essential hypertension but apparently is not reflected in abnormal function of the peripheral sympathetic nervous system in these patients.
Adult↗
Correction of hypokalemia by magnesium repletion in familial hypokalemic alkalosis with tubulopathy.
The effect of magnesium treatment on serum potassium and potassium balance was examined in three siblings with a recently described syndrome of hypokalemic alkalosis with renal tubulopathy. Oral magnesium supplementation for 11 days in the three siblings increased mean serum potassium from 2.7 +/- 0.1 meq/liter to 3.3 +/- 0.2 meq/liter (p less than 0.05). In addition, urinary and fecal potassium excretion decreased by about 11 meq/day. Magnesium chloride did not affect plasma renin activity while the patients were supine or upright. In contrast, mean supine plasma aldosterone concentration increased from 5.3 +/- 1.5 ng/dl to 13.2 +/- 4.1 ng/dl (p greater than 0.1) and mean upright plasma aldosterone concentration increased from 17.4 +/- 3.8 ng/dl to 66.1 +/- 7.3 ng/dl (p less than 0.01). These findings suggest that hypokalemia and potassium loss in this disorder may be caused by abnormal magnesium metabolism. The increase in plasma aldosterone concentration may have been caused by the positive potassium balance or a direct effect of magnesium on aldosterone secretion from the adrenal gland.
Adolescent↗
Reporting of phosphate and phosphorus plasma values.
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Humans↗
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.
Adult↗
Acute effects of dietary protein on calcium metabolism in patients with osteoporosis.
Five untreated osteoporotic patients were studied in a metabolic unit for 30 days while receiving control (0.8 gm/kg) and high (2.0 gm/kg) protein diets of purified proteins. The high protein diet increased urinary calcium and produced a negative calcium balance without causing significant change in calcium absorption, serum chemical values, or urinary sodium and potassium. Variable effects of calcium and/or estrogens were found on the negative balance. Hence, increased dietary protein acutely causes a negative calcium balance in osteoporotic patients and may contribute to bone loss in this disease.
Calcium↗