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F H Epstein

Publications and source records attributed to F H Epstein.

At least 127 records · Page 7Linked to original sources
PubMed1986

Cyclic AMP-dependent stimulation of Na,K-ATPase in shark rectal gland.

Scatchard analysis of 3H ouabain bound to isolated rectal gland cells as a function of increasing ouabain concentrations produced a concave curvilinear plot that was resolved into two specific sites with either a high (I) or low (II) affinity for ouabain. Cyclic cAMP/theophylline (+/- furosemide, 10(-4) M) increased the amount of 3H ouabain bound to the high-affinity site I. Vanadate, a phosphate congener which promotes formation of the ouabain-binding state of the enzyme, mimicked the effects of cAMP/theophylline at low concentrations of ouabain, suggesting that cAMP/theophylline increases binding to site I by enhancing the rate of turnover of resident enzyme. Enhanced 86Rb uptake seen following cAMP/theophylline administration was primarily associated with increased flux through the high-affinity ouabain site, and this stimulation was not obliterated by the co-administration of furosemide. A model was presented which suggested the presence of two noninteracting pools of enzyme or isozymes which exhibit either a high or low affinity for ouabain. Cyclic AMP both stimulated turnover via site I, and modified the kinetics of binding of 3H ouabain to site II. The (ave) Kd of 3H ouabain for site II was increased from 3.6 microM (controls) to 0.5 microM (cAMP/theophylline) and the Hill coefficient was modified from 0.45 (controls) to 1.12 (cAMP/theophylline), suggesting a transition from a negative- to a noncooperative binding state. While furosemide reversed the effects of cAMP/theophylline on site II kinetics, it did not obliterate cAMP/theophylline effects on site I. This suggests that cAMP may alter the intrinsic turnover rate of this particular pool of Na,K-ATPase in shark rectal gland.

Animals↗
PubMed1986

[Salt and blood pressure].

Current information on the relationship between sodium and blood-pressure regulation is reviewed from the point of view of epidemiological, clinical and experimental research, as well as evidence from intervention studies. Among other cations, calcium also has an influence on blood pressure. Epidemiological studies in particular are handicapped by the difficulties inherent in measuring salt intake in individuals with adequate accuracy. Despite remaining uncertainties and the need for further investigation, available data from different sources and a considerable number of studies justify the recommendation that the average daily salt intake of the population should not exceed 5 g (NaCl), corresponding to 85 meq or mmol of sodium (Na). This is a goal which should be approached gradually, paying simultaneous attention to other factors likely to be involved in the primary prevention of hypertension, especially overweight, and the maintenance of a sufficient supply of iodine and fluor for which salt is used as a vehicle in many countries.

Blood Pressure↗
PubMed1986

Differential responsiveness of proximal tubule segments to metabolic inhibitors in the isolated perfused rat kidney.

Rat kidneys were perfused for 90 minutes with cyanide, rotenone, antimycin, 2-deoxyglucose, or combinations of rotenone or antimycin with 2-deoxyglucose in oxygenated Krebs-albumin medium. Following perfusion, proximal tubule injury was evaluated by light microscopy. The types of lesions seen were similar to those previously reported after hypoxic perfusion and included brush border clubbing/mitochondrial swelling in S1 and S2 and cytoplasmic edema or cell fragmentation in S3. This finding supports the contention that these lesions represent characteristic responses of these segment types and that the S3 response differs from that in S1 and S2. S1 appeared most vulnerable to low dose cyanide or inhibition of mitochondrial electron transport (rotenone, antimycin). Inhibition of glycolysis (2-deoxyglucose) only produced injury in S2 tubules. With high dose cyanide or a combination of 2-deoxyglucose with either rotenone or antimycin, there was diffuse proximal tubule damage. Thus S3 appeared more resistant than the convoluted tubular segments to both inhibition of glycolysis and to inhibition of mitochondrial electron transport. This finding stands in contrast to the selective vulnerability of the S3 segment in ischemic renal injury.

Animals↗
PubMed1986

Hypoxic injury in the proximal tubule of the isolated perfused rat kidney.

The effect of hypoxia on the morphology of the proximal tubule was examined in isolated rat kidneys perfused with Krebs-albumin medium, gassed with 95% N2/5% CO2 for 45, 90 and 190 min. The major findings were heterogeneity of types of cell injury and definable topographical zones of protection from damage. The characteristic injury in S1 and S2 was that of mitochondrial swelling and brush border alterations that progressed to complete disorganization of this zone. S3 manifested two distinct lesions, one characterized by cell swelling and the other by tubular epithelial fragmentation. Protection from these injuries was seen in tubules located in periarterial zones, apparently due to gradients of oxygenation. The same types of injury but without zones of protection were seen after perfusion with cyanide (10 mM) in oxygenated medium. A "reflow" period of oxygenated perfusion did not alter the fundamental character of these lesions but affected tubules showed progression of damage while there was preservation of tubules in periarterial areas. Thus the responses of the proximal tubule to hypoxic injury depends both on segment type (S1, S2 versus S3) and on tubular location in relation to O2 availability. Additional factors appear to determine the type of response in S3 tubules.

Animals↗
PubMed1986

Transport-dependent cell injury in the S3 segment of the proximal tubule.

Two distinct types of injury, cytoplasmic edema and cell fragmentation occur in the S3 segment of the proximal tubule in isolated hypoxic perfused rat kidneys (Krebs-albumin medium gassed without O2). The proportion of S3 tubules with fragmentation strongly correlated with the GFR and urine output during the perfusion, and approached 100% when the GFR was increased by high perfusion pressure. Conversely, the fragmentation lesion was absent and the edema lesion extensive when tubular transport was inhibited by perfusion with hyperoncotic medium to prevent glomerular filtration or by addition of ouabain (10(-2) M) to the perfusate. Polyene antibiotics increase membrane permeability and thus the work of active electrolyte transport. Perfusion with amphotericin (3 X 10(-5) M) or nystatin (200 U/mliter) in oxygenated medium also produced fragmentation in S3. The lesion was prevented in the non-filtering kidney. Ouabain completely eliminated the cell fragmentation due to nystatin and significantly reduced that due to amphotericin. These results suggest that the injury of cell fragmentation is enhanced by transport activity and diminished when transport is inhibited. The edema lesion appears fundamentally different and more akin to lesions described in ischemia where tubular flow is absent, active transport is diminished, and the morphologic changes appear related to loss of cell volume regulation. The type of hypoxic damage exhibited by proximal tubular S3 segments may therefore be conditioned by active ion transport of tubular cells.

Amphotericin B↗
PubMed1986

Substrates induce hypoxic injury to medullary thick limbs of isolated rat kidneys.

Under certain conditions, excess of substrates may be detrimental to the kidney. In isolated rat kidneys perfused with cell-free medium, oxidative metabolism to support reabsorptive transport in the presence of a limited oxygen supply results in hypoxic injury to medullary thick ascending limbs (mTAL). Since inhibitors of mitochondrial respiration markedly reduced this injury, we evaluated the effects of altering the availability of substrate for oxidative metabolism in the mTAL. Inhibition of glucose utilization with 2-deoxyglucose (50 mM) and simultaneous inhibition of long-chain fatty acid metabolism with 2-tetradecylglycidic acid (10(-4) M) in the absence of exogenous substrates consistently reduced hypoxic cell injury to mTAL. Similarly, the direct inhibition of substrate oxidation by the citric acid cycle with monofluoroacetate (5 mM) also reduced the extent of damage to this nephron segment. Bypassing these metabolic blockades with L-lactate, pyruvate, or alpha-ketoglutarate stimulated renal oxidative metabolism and increased hypoxic damage to mTAL. Enhanced renal metabolism and function (higher renal oxygen consumption, tubular reabsorption of sodium, and glomerular filtration rate) were paradoxically associated with greater damage to mTAL. Thus, when oxygen supply is limited, substrate-supported aerobic metabolic activity for tubular transport may induce hypoxic injury in the renal medulla.

Animals↗
PubMed1986

Lactate increases potassium secretion by perfused rat kidney.

The effect of exogenous metabolic substrates on K+ secretion was evaluated in the isolated perfused rat kidney in the presence of 2-deoxyglucose and 2-tetradecylglycidic acid to inhibit utilization of glucose and fatty acids from endogenous sources. L-Lactate (15 mM) added to the perfusion medium enhanced renal oxygen consumption (4.0 +/- 1.1 mumol X min-1 X g-1 vs. 2.0 +/- 1.0 without lactate) while decreasing fractional excretion of sodium (19.3 +/- 2.4% vs. 47.3 +/- 1.8). L-Lactate markedly increased the fractional excretion of K+ to 181 +/- 29% compared with 68 +/- 12% without lactate (P less than 0.001). The poorly metabolized isomer D-lactate did not alter these parameters. The addition of alpha-ketoglutarate only slightly increased K+ excretion. In the absence of metabolic inhibitors and in the presence of glucose (5 mM), L-lactate also increased K+ excretion significantly more than did D-lactate (108 +/- 19% vs. 69 +/- 11, P less than 0.02). At the end of 90 min of perfusion with L-lactate medium, K+ concentration in the perfusate dropped from 4.7 +/- 0.05 to 3.2 +/- 0.2 meq/liter (vs. 3.8 +/- 0.1 meq/liter with D-lactate, P less than 0.005) without differences in glomerular filtration rate or sodium excretion. L-Lactate appears to increase K+ secretion by preferential metabolic stimulation of the distal tubule, a process that may help in vivo to prevent hyperkalemia in lactic acidosis.

Amiloride↗
PubMed1986

The effect of age and sodium depletion on cardiovascular response to orthostasis.

To test the hypothesis that normal age-related limitations in cardiovascular homeostasis may become clinically significant under stress, the cardiovascular response to postural change was assessed in six young and six old healthy subjects before and after modest diuretic-induced sodium depletion. Before diuresis, systolic blood pressure was maintained (from 110 +/- 4 to 113 +/- 6 mm Hg) while heart rate increased 22% (from 67 +/- 2 to 82 +/- 5 beats/min) at 3 minutes after 60-degree upright tilt in young subjects. After a significant diuretic-induced weight reduction and natriuresis, the young again maintained systolic blood pressure (from 110 +/- 4 to 110 +/- 6 mm Hg) and increased heart rate 49% (from 68 +/- 2 to 101 +/- 5 beats/min; p less than 0.05, compared with prediuresis values) in response to the same postural stimulus. During the prediuresis tilt, the older subjects showed no change in systolic blood pressure (from 132 +/- 4 to 134 +/- 6 mm Hg) and a 9% increase in heart rate (from 68 +/- 3 to 74 +/- 2 beats/min). After a similar significant weight reduction and sodium loss, the older subjects showed a significant reduction in systolic blood pressure (from 132 +/- 6 to 108 +/- 6 mm Hg; p less than 0.05) and a 17% increase in heart rate (from 69 +/- 4 to 81 +/- 3 beats/min; p less than 0.05) during tilt compared with values in young subjects. Three of six elderly subjects noted postural symptoms. These results suggest that, although the healthy old may appear well compensated under optimal conditions, decreased cardiovascular reserve renders them susceptible to postural change following mild sodium depletion.

Adult↗
PubMed1986

Effect of protein ingestion on urinary dopamine excretion. Evidence for the functional importance of renal decarboxylation of circulating 3,4-dihydroxyphenylalanine in man.

Since dietary protein increases urinary dopamine (DA) excretion in animals, this study was undertaken to assess the role of DA production in the acute changes in renal function following protein ingestion in man. Excretion of DA, sodium, potassium, water, solute, and creatinine were measured in six normal men in 30-min intervals over 5 h after oral ingestion of protein and/or carbidopa, an inhibitor of DA formation from 3,4-dihydroxyphenylalanine (DOPA). Overall, protein increased urinary DA 50% (P = 0.031) while carbidopa reduced it 70% (P less than 0.0001), although suppression of DA excretion by carbidopa was not uniform over the 5 h of observation. Carbidopa doubled the level of DOPA in venous plasma and greatly magnified the DOPA response to protein. Inhibition of decarboxylase activity reduced excretion of sodium, potassium, solute and water after protein ingestion. These results indicate that extraneuronal DOPA decarboxylation in kidney contributes to acute protein-induced changes in renal function in man and suggest a general role for the decarboxylation of circulating DOPA in the expression of dopaminergic effects on the kidney in vivo.

Adult↗
PubMed1986

Physiologic increase and tracking of blood pressure in schoolchildren.

4343 blood pressure (BP) recordings were obtained in 1575 schoolchildren during 5 years. Systolic BP rose proportionally to upper arm muscle area (MA) in both sexes. In contrast, upper arm fat area (FA) was considerably lower in boys than in girls, and the rise of systolic BP in boys during puberty was not accompanied by any increase of FA. At repeat examination of 900 children after 1 to 5 years, between 35% and 53% of those with initial systolic BP in the highest quintile had again values in the same quintile, thus twice as often as expected. Tracking in the highest decile was even stronger: 37% of 82 children had again systolic BP in the highest decile at 2 years, and 29% at 4 to 5 years. We conclude that the physiologic increase of systolic BP is primarily determined by rising muscle mass, and tracking still remains detectable in children after 4 to 5 years and is strongest in those with highest values.

Adipose Tissue↗
PubMed1986

Isolated rectal gland cells: oxygen consumption and hormonal stimulation.

Cells isolated from rectal glands of Squalus acanthias, using collagenase and hyaluronidase digestion, retained normal morphological characteristics as judged by light microscopy of 1-micron plastic sections. Their oxygen consumption per unit weight was comparable to that of intact rectal gland studied either in situ, or by isolated perfusion, as well as that of rectal gland slices. Cellular respiration was stimulated by dibutyryl cyclic AMP and theophylline or by vasoactive intestinal peptide which stimulate secretion of chloride by the intact gland. Stimulated oxygen consumption was inhibited by ouabain and bumetanide and was proportional to the concentration of sodium or chloride in the incubation solution. The oxygen consumption of these cells parallels the secretory and metabolic behavior of the intact rectal gland, suggesting that it reflects energy demands for ion transport. The relative ease with which a homogeneous preparation of viable and active cells can be obtained and the apparent preservation of many of their key functional characteristics make this preparation a useful tool for the study of hormone-stimulated ion transport.

Adenosine↗
PubMed1986

Inhibition of prostaglandin synthesis in rat kidney perfused with and without erythrocytes: implication for analgesic nephropathy.

A marked defect in renal concentration ability associated with hypoxic lesions in the medullary thick ascending limb (mTAL) characterizes the isolated rat kidney perfused with cell-free solutions. Addition of erythrocytes to the perfusion medium, a maneuver known to eliminate signs of hypoxic cellular injury to mTALs, greatly improved renal concentrating ability. When indomethacin was given to kidneys perfused with erythrocyte-enriched medium, concentrating ability was further improved by the drug to an average U/Posm of 2.45 +/- 0.81, and medullary cellular structure remained normal in appearance. Since renal hypoperfusion predisposes to acute renal failure from non-steroidal antiinflammatory drugs (NSAIDs) and medullary ischemia might play a role in chronic analgesic nephropathy, a synergism between NSAIDs and medullary hypoxia was evaluated in the isolated perfused rat kidney. Indomethacin and naproxen added to the perfusion medium (at 10(-4) and 5 X 10(-4) M, respectively) effectively depressed prostaglandin E2 (PGE2) production by the isolated kidney but did not improve its concentrating ability when perfused with cell-free medium. Quantitation of hypoxic injury to mTALs, regularly observed in this model, indicated that both indomethacin and naproxen increased the extent and severity of damage in the deeper, most hypoxic portions of the inner stripe. Addition of PGE2 to cell-free perfusate reduced the extent of hypoxic damage to the mTAL. These results suggest that in medullary hypoxia, prostaglandins protect mTAL cells by either vasodilatation or reduction in active transtubular transport. NASAIDs, by suppressing prostaglandin production, could predispose the renal medulla to hypoxic injury.

Amino Acids↗
PubMed1986

Studies of atherosclerosis determinants and precursors during childhood and adolescence.

At a Meeting of Investigators on Epidemiological Studies of Atherosclerosis Determinants and Precursors, which was held in Geneva on 7-9 November 1983, representatives from 26 countries reviewed the current status of epidemiological studies in this area. Particular interest was shown in the following determinants of cardiovascular disease: blood pressure, blood lipid levels, body weight, pathological studies, and tobacco use. Working papers on each determinant were prepared, and recommendations were made on areas for research, and on the need for prevention programmes and pathological studies. This article summarizes the work of the meeting.

Adolescent↗
PubMed1986

Hyperkalemia.

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Acid-Base Equilibrium↗
PubMed1986

Sudden death--epidemiological aspects.

Coronary heart disease presents in a disturbingly high percentage of instances as sudden death. A large percentage of cases occur outside the hospital, outside the reach of emergency care. Data on the frequency of sudden death, within the framework of coronary heart disease incidence, are presented. The risk factors for sudden death, as far as it is known, are similar in kind and predictive power to those for myocardial infarction with survival. While there is a great need for new tests which predict susceptibility to sudden death with adequate sensitivity and specificity, the lesson to be learned from all the knowledge already gained is that prevention of premature coronary heart disease as a whole, through appropriate changes in life style, will correspondingly reduce the risk of sudden death in the population as well. This knowledge must be put into action and should have an appreciable effect on the frequency of sudden death while more research on the mechanisms of the condition is being conducted.

Adult↗
PubMed1986

Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney.

The topography of renal injury after ischemia-reflow was studied in intact rats by clamping the right renal artery for variable periods of time and examining the histologic appearance of the kidney in large 1-mu plastic sections. As reported by others, the straight portion of the proximal tubule (S3) was especially susceptible to ischemia-reflow injury. The pattern of focal necrosis produced in S3 by short (15-30-minute) and longer (45-60-minute) periods of arterial occlusion appeared related to gradients to oxygenation during reflow, in that more extensive injury was seen in areas remote from blood vessels, while perivascular tubules were protected. A similar pattern was seen in S1 and S2 after a longer period (45-60-minutes) of ischemia, which produced extensive but incomplete necrosis in these convoluted segments, with protected tubules lying within zones surrounding arcuate and interlobular arteries. The immediate postglomerular portion of S1, a tubular segment normally well supplied with oxygen, was an exception to this rule. Selective necrosis limited to this portion of the nephron appeared after only 15-30 minutes of ischemia, recalling the special sensitivity of S1 cells to inhibition of mitochondrial respiration. These results suggest that in different segments of the proximal tubule, injury after ischemia-reflow is determined not only by changes that occur during complete ischemia but also by the adequacy of oxygenation during the reflow period.

Animals↗
PubMed1985

Catecholamine modulation of rapid potassium shifts during exercise.

Plasma potassium rises during muscular exercise and falls rapidly when exercise is stopped. Since the sympathoadrenal system is stimulated with exertion and both alpha- and beta-adrenergic agonists affect internal potassium homeostasis, we studied the influence of catecholamines on potassium shifts during and after exercise. Six healthy subjects were given maximal exercise stress tests under three conditions: with no medication (control), during beta-blockade with propranolol, and during alpha-blockade with phentolamine. Compared with a peak rise in plasma potassium of 1.23 +/- 0.27 mmol per liter (mean +/- S.E.M.) during the control study, propranolol caused a rise of 1.89 +/- 0.35 (P less than 0.01) and a sustained elevation during recovery. Phentolamine diminished the rise of potassium (0.70 +/- 0.21 mmol per liter; P less than 0.01) and lowered the potassium level throughout recovery. These effects of catecholamines were independent of the venous pH, the plasma bicarbonate and serum glucose levels, and urinary potassium excretion, and they did not appear to be due to insulin. High norepinephrine and epinephrine levels confirmed the release of catecholamines capable of stimulating alpha- and beta-receptors. Exercise work did not differ among the groups. beta-Adrenergic receptors appear to moderate the acute hyperkalemia of exercise, whereas alpha-adrenergic receptors act to enhance hyperkalemia and may protect against hypokalemia when exertion ceases.

Adrenergic alpha-Antagonists↗