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Biomedical subjects

F C Bartter

Publications and source records attributed to F C Bartter.

At least 109 records · Page 6Linked to original sources

Role of steroids in hypertension: evaluation of plasma mineralocorticoid activity with aldosterone receptors.

1. A competitive "mineralocorticoid" receptor-binding technique has been used to study plasma "mineralocoroticoid" activity in normal and hypertensive states. The binding reaction mixture contains the competitor steroids in undiluted plasma, [3H]aldosterone and rat kidney slices. Thus plasma binding and receptor occupancy can be simultaneously considered. 2. Competitor activities relative to that of aldosterone (100%) were: deoxycorticosterone (DOC), 16%, cortisol, 0-4%; 18-hydroxydeoxycorticosterone (18-OH-DOC), 0-1%; 16beta-OH-dehydroepiandrosterone and 16-oxo-androstenediol, inactive. (Binding characteristics for aldosterone and the other steroids tested with the rat receptor were found to be similar to those with receptors in slices from human kidney, obtained at operation.) These steroids and the spironolactone SC14266 were less active in plasma than in buffer, suggesting that they bind significantly to plasma and that reduces their capacity to occupy the receptors. 3. These competition data also suggest that at normal and even mildly elevated concentrations, cortisol does, but DOC and 18-OH-DOC do not, contribute significantly to the plasma mineralocorticoid activity. Competitor activity in plasma samples taken at 12.00 hours from normal subjects (upright) was greater than that in those taken at 08.00 hours (supine). This physiological change, corresponding to an increase in aldosterone, was detected even though there was an associated decrease in plasma cortisol. Competitor activity in plasma from patients with primary aldosteronism was markedly elevated as compared with that of normal subjects. However, an increase in plasma steroids which bind to the mineralocorticoid receptor was not detected in plasma from patients with "low-renin essential hypertension".

Aldosterone↗

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.

Animals↗

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.

Aldosterone↗

The circadian periodicity of urinary 17-ketosteroids, corticosteroids, and electrolytes in congenital adrenal hyperplasia.

The circadian periodicity of adrenal function in patients with congenital virilizing adrenal hyperplasia (CAH) was examined by measuring the urinary 17-ketosteroids, 17-hydroxycorticosteroids, sodium, and potassium. Patients with the salt-losing and the non-salt-losing types were studied with and without treatment. Cosine curves were fitted to the data by the least-squares method to determine the mesors, amplitudes, and acrophases of the variable for each patient. The data reveal distinct circadian rhythms for all variables measured whether or not the patient was receiving treatment. The acrophases for 17-ketosteroids and 17-hydroxycorticosteroids were between 1500 and 1800 h. These acrophases are about 6 h later than those for normal subjects. The treatment on a fixed daytime schedule for many years may have shifted the natural rhythm.

17-Hydroxycorticosteroids↗

17 alpha estradiol: separation of estrogen effect on collagen from other clinical and biochemical effects in man.

In rodents the effect of 17alpha estradiol upon collagen is identical to that of 17beta estradiol, but the 17alpha estradiol effect upon uterine lining is 1/1000 that of 17beta estradiol. Both steroids reverse the effect of D-penicillamine on rodent skin collagen. Five human beings with the skin collagen changes associated with D-penicillamine were treated with 17alpha estradiol for three to six weeks. 17alpha estradiol caused no detectable changes in blood pressure, breast development, menstrual periods, serum liver enzymes, serum proteins, plasma growth hormone, insulin, serum clotting factors, serum triglycerides, serum copper or serum ceruloplasma. In contrast, 17alpha estradiol increased skin prolyl hydroxylase activity, increased soluble collagen content in the skin and increased urinary hydroxyproline excretion. These studies with 17alpha estradiol, point out a specificity difference between the various sites of estrogen action in human beings.

Collagen↗

Prostaglandins are overproduced by the kidneys and mediate hyperreninemia in Bartter's syndrome.

In summary, the cardinal features of the syndrome of renal juxtaglomerular hyperplasia include overproduction of plasma renin activity, elevation of plasma angiotensin II concentration, elevation of aldosterone secretion and of plasma aldosterone concentration, hypokalemic alkalosis, and a resistance of arterioles to the pressor action of angiotensin II and norepinephrine. In the present studies, elevation of urinary PGE2 but not of PGF2alpha has been demonstrated. Inhibition of prostaglandin synthetase with indomethacin or ibuprofen has been shown to decrease plasma renin activity, and plasma aldosterone concentration and secretion rate, leading to a positive potassium balance and restoration of normal plasma potassium. The inhibitors decreased and glomerular filtration rate, and induced sodium retention. The results indicate that overproduction of PGE by the kidneys is a cardinal feature, but not necessary the primary one, in the pathogenesis of this syndrome.

Adolescent↗

Effects of calcium infusions in patients with postmenopausal osteoporosis.

From earlier studies, it appeared that postmenopausal women with osteoporosis may not be so responsive to therapeutic calcium infusions as younger men. A study of seven women with postmenopausal osteoporosis revealed that only one had a good therapeutic response as judged by sustained decrease in bone pain and improvement in calcium balance. It is concluded that a series of calcium infusions is unlikely to be therapeutically useful in postmenopausal osteoporosis.

Aged↗

The development and application of a radioimmunoassay for 18-hydroxy-corticosterone.

A sensitive and specific radioimmunoassay has been developed for 18-hydroxy-corticosterone (18-OH-B) and applied to the measurement of this steroid in peripheral plasma. High specific activity label (3H-18-OH-B) was prepared using the incubation of 3H-corticosterone with duck adrenal mitochondria. Antisera were produced by immunisation with 18-OH-B gamma-lactone 3-oxime conjugated to bovine serum albumin. The antibodies examined showed 100% cross-reactivity with 18-hydroxy-deoxycorticosterone gamma-lactone (18-OH-DOC gamma-lactone), but minimal cross-reactivity with other steroids. Paper chromatography was used to separate 18-OH-DOC gamma-lactone from 18-OH-B gamma-lactone. The interassay precision was 7.6% and the intra-assay precision 11.0%. The accuracy of the method was confirmed by showing a linear relationship between amounts of 18-OH-B added and amounts of 18-OH-B gamma-lactone measured (y = 0.854 X +15.1, r = 0.9. p less than 0.001). The mean plasma level in normal subjects on an ad libitum sodium intake was 225 +/- 92.7 (SD) pg/ml (n = 17) when standing, and 99 +/- 38.3 (SD) pg/ml (n = 6) after lying down for 30 minutes.

18-Hydroxycorticosterone↗

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.

Adolescent↗

Effect of spironolactone on sex hormones in man.

Administration spironolactone at a dosage of 400 mg/day to healthy male volunteers for 5 days resulted in a significant rise in plasma progesterone and 17alpha-hydroxyprogesterone which persisted throughout the study. A transient increase in plasma FSH and LH concentration was observed after the second but not the third or fifth days of drug administration. There was no change in plasma concentration of testosterone, 17beta-estradiol, or prolactin. These findings are consistent with a previously-reported spironolactone-induced destruction of the microsomal enzyme cytochrome P-450, an enzyme necessary for 17-hydroxylase and desmolase activity. The results do not explain the decrease of libido, the impotence, and the gynecomastia frequently associated with spironolactone therapy in males.

17-Ketosteroids↗

Gout as a complication of Bartter's syndrome. A possible role for alkalosis in the decreased clearance of uric acid.

A prevalence of hyperuricemia of 50% and of acute gouty arthritis of 20% has been observed in a group of patients with Bartter's syndrome. All patients except one presented initially with complaints unrelated to uric acid metabolism. The cause of their hyperuricemia and subnormal clearance of uric acid is unexplained. Systemic alkalosis, a prominent feature of Bartter's syndrome, can decrease the clearance of uric acid and may contribute to the hyperuricemia and gout that have been observed. Physicians should be aware of the possibility of gout as a clinical complication of Bartter's syndrome and of the inhibitory effects of alkalosis on urate clearance.

Acute Disease↗

Pituitary stones.

Two cases of patients having calcification within the sella turcica (pituitary stones) have been studied and followed up, one patient for 18 years. A detailed analysis of the radiographic findings and endocrinologic profiles of these two patients is presented. The rarity of bona fide pituitary stones and their benign nature, as evidenced by the two cases reported here, are emphasized.

Adult↗