J. C. Beck

Essential Hypertension and Aldosterone

Serial determinations of the urinary excretion of aldosterone have been made in hypertensive patients. Although the majority of patients with benign essential hypertension excrete amounts of aldosterone within the normal range, the mean excretion of 26 patients was significantly higher than that observed in normotensive individuals. When renal complications were present, the mean excretion was still further increased and in patients with malignant hypertension all the values were above the normal range. The mean excretion of the tetrahydro metabolite of aldosterone was also found to be higher in patients with essential hypertension. These patients have a normal response to adrenocorticotrophic hormone stimulation, urinary and plasma corticosteroids, as well as urinary aldosterone, showing comparable increases. The aldosterone content of adrenal glands obtained post mortem from two patients with malignant hypertension was within the range observed by other investigators in primary aldosteronism.

Conversion of glucose to lipid by human adipose tissue in vitro

Abstract The rates of incorporation in vitro of glucose carbons into carbon dioxide and glyceride-glycerol and fatty acids by specimens of omental adipose tissue obtained from patients undergoing elective surgery were studied in the absence and presence of insulin. The basal (absence of insulin) activity for each parameter of glucose metabolism in the individual specimens correlated significantly with the insulin-stimulated increments. The glucose metabolism of specimens of subcutaneous adipose tissue, obtained under local anesthesia from normal volunteers in the fasting state and after ingestion of a standard breakfast, was also studied. In the absence of added insulin the incorporation of the glucose carbons into glyceride-fatty acids was consistently greater in specimens obtained after feeding, but incorporation into carbon dioxide and glyceride-glycerol was not significantly increased. In the presence of maximally effective amounts of insulin, there was no significant difference between the elevated rates of incorporation of glucose carbons into carbon dioxide and glyceride-glycerol and fatty acids between the specimens obtained before and after feeding. It was concluded that feeding did not enhance the maximal capacity for lipogenesis in adipose tissue. The modest increase in glyceride-fatty acid production in specimens obtained after feeding was probably due to effects of endogenous insulin. A hypothetical rate of lipogenesis from glucose derived from these data suggests that the production of fatty acids from glucose in human adult adipose tissue occurs on a very small scale relative to the intake of carbohydrate in normal man.

Factors affecting lipid synthesis in human adipose tissue in vitro

Incorporation of glucose into total lipids in vitro by human omental and subcutaneous adipose tissue obtained at laparotomy was increased by prior intravenous infusion of glucose. The greatest increase occurred in the fatty-acid moiety. Oxidation in vitro of glucose labeled at carbon-1 or carbon-6 to CO2 by tissues from infused patients gave a C-1C-6 ratio which resembled that seen when tissues from non-infused patients were incubated with insulin. Lipid synthesis by tissues from different patients varied from 2000 mμmoles glucose incorporated per Gm. total lipid. Increasing the time of incubation increased the rate of lipogenesis from glucose and acetate, except when lipid synthesis was extremely rapid. Lipogenesis from glucose increased when the concentration of glucose in the incubation medium was increased and in the presence of insulin but decreased in the presence of epinephrine; in the latter case the synthesis of glyceride-glycerol from glucose was increased.

Malignant hypertension and aldosterone secretion: Influence of reversal and progression of the syndrome in two cases

Abstract Rates of secretion of aldosterone, measured by an isotopic dilution method using 7-H 3 -d-aldosterone, are reported in two patients with malignant hypertension during the period of progression and regression of the malignant phase. Hyperaldosteronism in the malignant phase appears to be a secondary phenomenon, and its maintenance may depend upon the renal lesion of the malignant phase.

THE DIURNAL RHYTHM OF URINARY ELECTROLYTE EXCRETION. II. IN CERTAIN DISEASE STATES.

Abstract Data are presented of the diurnal rhythm of urinary sodium, potassium and chloride excretion in patients with disease involving the brain, brain stem, spinal cord, renal nerves and adrenal glands. No patient had significant impairment of cardiac or renal function. Normal rhythms were observed after adrenalectomy (on maintenance of 17-hydroxycorticosteroid), renal denervation and in one patient with quadriplegia. Electrolyte excretory rhythms were absent in patients with disease of upper cervical cord, brain stem and reticular system, although these patients had normal sleep-wake cycles; diurnal rhythmicity was also absent in 2 unconscious patients. It is believed that these rhythms are under control of subcortical parts of the brain; e.g., hypothalamus, and are not effected primarily by adrenal or neuronal pathways.

STUDIES WITH ANTISERA TO PITUITARY HORMONES.

Summary (1) Specific antisera to hormones have been used to elucidate specificity of biological activity in an in vitro system. (2) Fluorescein-conjugated antisera have been used to localize hormones in human pituitary tissue. Certain cells were found to fluoresce with both antisera to ACTH and to TSH. Several immunochemical technics failed to demonstrate a cross-reaction to explain this finding. An hypothesis has been suggested to explain conflicting reports of localization of hormones in the pituitary.

Renal clearance studies of the 17-hydroxycorticosteroids

Abstract The protein-bound and non-protein-bound moieties of the free 17-hydroxycorticosteroids (17-OHCS) and the 17-hydroxycorticosteroid-glucuronides (17-OHCS-Glucuronides) of plasma have been determined utilizing the technic of equilibrium dialysis. Renal clearance studies have been carried out in three normal and three totally adrenalectomized subjects. The renal clearance of the non-protein-bound free 17-OHCS has not been shown to definitely exceed the simultaneous inulin clearance while the clearance of the non-protein-bound 17-OHCS-Glucuronides has been variably found to be in excess of the glomerular filtration rate. From these observations it would seem that the free 17-OHCS are handled by glomerular filtration and tubular reabsorption while there is suggestive evidence for bidirectional tubular transport of the 17-OHCS-Glucuronides. Bidirectional tubular transport of the free 17-OHCS cannot be excluded by this study.

Metabolic Effects of Human Growth Hormone

Publisher Summary This chapter discusses the study of metabolic actions of human growth hormone (HGH). The metabolic actions of HGH may be considered in four broad categories: anabolic effects, skeletal effects, effects on carbohydrate and fat metabolism, and miscellaneous effects. These are artificial division but such a categorization simplifies the presentation of the numerous metabolic effects of growth hormones. Any hypothesis of the mechanism of action of HGH must integrate the wide variety of metabolic response to the hormone and the time course over which they occur and, finally, must take into account the relative impotence of HGH in vitro. It has been found that the individuals lacking HGH but with exaggerated insulin response to glucose and arginine are resistant to exogenous insulin and HGH. Individuals with insulinopenia and sensitivity to exogenous insulin but with normal or abnormally high plasma HGH levels show little or no response to exogenous HGH. The simplest postulate would be that either growth hormone itself is altered to produce sulfation factor or it acts with a substrate to produce sulfation factor that in turn acts on the end organ.

Heterogeneity of antisera to human growth hormone, demonstrated by the immunofluorescence technique.

Earlier studies (1) showed the fluorescein-conjugated antisera to human growth hormone (HGH) localized in acidophils of human, rat, and bovine pituitary glands, and that the fluorescence, which was inhibited when the specific antigen or the unconjugated antisera was applied before staining, was specific. During inhibition studies, one batch of anti-HGH (titer, 1/12,000: batch HGH-5) inhibited fluorescence caused by another batch of fluorescein-conjugated anti-HGH (titer 1/25,000; Hg-1) in the human but not the rat pituitary gland. Inhibition was repeated with anti-HGH batch HGH-5 and followed by 1:2 and 1:3 dilution of fluorescein-conjugated anti-HGH Hg-1 (which still produced fluorescence); again, fluorescence was not inhibited in the rat pituitary. However, when conjugated and unconjugated anti-HGH Hg-1 from the same batch were used, staining was completely inhibited in both rat and human pituitaries. The present studies were carried out to determine the cause of this discrepancy. Materials and Methods. The immunofluorescent-staining method used was described previously (2). Preparation of antisera to HGH from 9 rabbits and 1 guinea pig were used for inhibition experiments. Fluorescein-conjugated anti-HGH Hg-1 and Hgh-5, which were used as staining antisera, produced bright fluorescence in rat, human, and bovine pituitaries. The titers were measured by the bis-diazotized benzidine (BDB)-hemagglutination method. Results. Two antisera did not inhibit staining in any experiment (Table I and II). In human pituitaries, all others produced inhibition of variable degree. In rat, complete inhibition occurred with only two antisera (Table I). In bovine pituitaries, complete inhibition occurred with only one antiserum. Six antisera were conjugated with fluorescein (Table III); since the titer of antisera that failed to stain was unchanged after conjugation, activity was not destroyed during this procedure. Indirect staining, using fluorescein-conjugated sheep anti-rabbit gamma globulin, showed some degree of fluorescence with all eight antisera (Table IV). These experiments indicate that different rabbits may produce different antisera to a single antigen.

Aldosterone secretion rate and electrolyte balance studies on three patients with hypertension: Influence of guanethidine, hydralazine and methyclothiazide

Abstract The influence of 3 antihypertensive agents, guanethidine, hydralazine and a thiazide derivative was studied upon aldosterone secretion in 3 patients with hypertension maintained on a controlled dietary intake. Sodium restriction and methyclothiazide administration each alone did not cause an increase in aldosterone secretion rate. Aldosterone production rose when the 2 procedures were combined and the severe symptoms necessitated oral potassium supplements. The antihypertensive response secondary to administration of guanethidine and hydralazine did not increase aldosterone secretion, in fact a questionable fall was noticed. It is suggested that aldosterone response to sodium restriction and intravascular volume changes in certain hypertensive patients may quantatively differ from that of the normal subject.