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F H Epstein

Publications and source records attributed to F H Epstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

On the mechanism of the effects of potassium restriction on blood pressure and renal sodium retention.

Dietary potassium restriction increases sodium and chloride retention, whereas potassium administration promotes both diuresis and natriuresis. In epidemiologic and clinical studies, potassium intake is inversely related to blood pressure and is lower in blacks than in whites. The present studies examined the mechanism by which potassium restriction fosters sodium conservation and the impact of race on this response. Twenty-one healthy black and white men and women ingested an isocaloric, potassium-restricted diet (20 mmol/d) containing 180 mmol/d of sodium with and without a potassium supplement (80 mmol/d) for 9 days on two occasions. Additionally, eight of these subjects ingested the same diets for 3 days followed by a water load to determine free water clearance before and during the early phase of dietary potassium restriction. During potassium restriction, mean arterial pressure (MAP) derived from 24-hour blood pressure measurements was higher (85.7 +/- 1.6 mm Hg v 82.0 +/- 1.3 mm Hg; P < 0.001), cumulative sodium excretion lower (984 +/- 59 mmol/d v 1,256 +/- 58 mmol/d; P < 0.001), and weight greater (71.1 +/- 2.1 kg v 69.3 +/- 2.2 kg; P < 0.001). Blacks displayed no greater increase in MAP, although they excreted less sodium overall and less potassium on the potassium-supplemented diet. After a water load, minimum urine osmolality (Uosm) was lower (53.0 +/- 3.0 mOsm/L v 65.6 +/- 3.5 mOsm/L; P = 0.01) and free water clearance greater (4.44 +/- 0.59 mL/min v3.72 +/- 0.58 mL/min; P = 0.009) during potassium restriction. In conclusion, in healthy, normotensive subjects, potassium restriction was associated with an increase in blood pressure and volume expansion effected by increased renal sodium and chloride retention. Potassium restriction was also associated with increased free water clearance and enhanced diluting capacity consistent with augmentation of Na+, K+:2Cl- cotransporter activity in the thick ascending limb of Henle. This mechanism may play an important role in the renal adaptation required for potassium conservation, but at the expense of sodium chloride retention and an elevation in blood pressure.

Adult↗
PubMed1997

Transport mechanisms that mediate the secretion of chloride by the rectal gland of Squalus acanthias.

The rectal gland of Squalus acanthias secretes chloride by a mechanism that has been termed "secondary active transport" because it depends on the activity of Na-K-ATPase. As currently described, chloride enters the cell across the basolateral cell membrane via the 2 chloride: sodium: potassium cotransporter. The energy for this electroneutral uphill movement of chloride and potassium is provided by the gradient for sodium directed into the cell. Present in the basolateral cell membrane is Na-K-ATPase that maintains the gradient for sodium. A potassium conductance, present as well in the basolateral cell membrane, recirculates the potassium. Chloride exits the cell across the luminal membrane via CFTR, the chloride conductance. This mechanism is widely distributed throughout vertebrates. This report reviews the experimental observations that led to the current definition of the mechanism of chloride transport in the rectal gland.

Animals↗
PubMed1997

Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans.

Radiocontrast exposure is associated with vasoconstriction of the renal vascular bed and, in certain circumstances, with acute renal failure. This may be influenced by the volume of contrast infused or underlying disease, such as diabetes or renal failure. Changes in circulating vascular regulators, such as endothelin and atrial natriuretic peptide (ANP), may play a role in the development and/or prevention of acute renal failure. Nineteen patients undergoing arteriographic procedures were divided into two groups: large-volume contrast (> or = 150 mL; n = 7) and small-volume contrast (< 150 mL; n = 12). Circulating endothelin levels increased significantly (from 12.3 +/- 1.1 pmol/L to 19.4 +/- 2.2 pmol/L; P < 0.05) following large-volume contrast exposure (group 1) but not following small-volume contrast exposure (group 2) (13.9 +/- 1.7 pmol/L to 12.2 +/- 0.09 pmol/L). ANP levels increased significantly in both groups: 43 +/- 15 pg/mL to 75 +/- 21 pg/mL in group 1 and 33 +/- 16 to 106 +/- 39 pg/mL in group 2. Data from an additional eight patients with underlying diabetes mellitus and/or renal insufficiency also were obtained and were considered separately. Endothelin levels were higher at baseline and increased significantly after contrast (25.7 +/- 5 pmol/L to 55.4 +/- 18 pmol/L) despite the relatively small average volume of contrast infused (112 +/- 15 mL). ANP levels were also highest in these patients (211 +/- 43 pg/mL precontrast and 323 +/- 65 pg/mL postcontrast). No group had a significant change in serum creatinine following contrast exposure. In conclusion, large-volume radiocontrast exposure is associated with an increase in both circulating endothelin and ANP levels. Patients with underlying diabetes or renal insufficiency may have higher baseline levels and a greater tendency to increase endothelin after contrast exposure. While an increase in endothelin may contribute to renal vasoconstriction following radiocontrast exposure, simultaneous increases in ANP may serve to offset this response and protect against changes in renal function.

Adult↗
PubMed1997

Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work.

The isolated perfused rat kidney provides a model of selective hypoxia to the medullary thick ascending limb. To investigate the relationship between immediate early gene expression and the extent of hypoxic damage, we determined expression of the immediate early genes (IEG) c-fos and egr-1 in isolated perfused kidneys during standard perfusion and after various measures shown previously to be protective. mRNA levels of c-fos and egr-1 were markedly increased in kidneys after 90 minutes of standard perfusion with Krebs-Henseleit buffer containing albumin. Gene expression was most prominent in the outer medulla followed by papilla and cortex, a pattern reflected by the immunohistochemical demonstration of a prominent accumulation of both egr-1 and c-fos polypetides mainly in the medullary thick ascending limb (mTAL). Protective measures known to minimize morphological damage to the mTAL, including hyperoncotic perfusion, perfusion with glycine, or perfusion with a mixture of amino acids, decreased mRNA levels of c-fos and egr-1 in the outer medulla (by 50% and 35%, respectively) and the papilla (by 60 and 30%, respectively). Renal cortex showed only minor changes. In contrast, prevention of tubular transport by perfusion with 1 mM ouabain increased mRNA levels of c-fos and egr-1 in the outer medulla by 100% and 60%, respectively. Ouabain also dramatically increased mRNA levels of both IEGs in two lines of cultured renal epithelial cells. Changes in the level and distribution of the protein products of these IEGs were not detectable in perfused kidneys by immunohistochemistry. Hypoxic injury of the kidney stimulates IEG expression even in the absence of reperfusion. Protection against hypoxic injury in the mTAL correlates with suppression of IEG mRNA levels when protection is provided by amino acids or hyperoncotic perfusion, but not when provided by inhibition of Na,K-ATPase, which stimulates IEG expression. We conclude that diminished IEG expression is not a necessary concomitant of protection against hypoxic injury.

Amino Acids↗
PubMed1997

Urinary cyclic GMP, endothelin, and prostaglandin E2 in normal pregnancy and preeclampsia.

Cyclic GMP, endothelin and prostaglandin E2 (PGE2) all have systemic vasoactive properties (with cyclic GMP acting as a second messenger of nitric oxide). Intrarenally they act as natriuretics and urinary levels reflect intrarenal production. Cyclic GMP and PGE2 also act as important inhibitors of platelet activation and thrombosis. The purpose of this study was to determine if urinary levels of cyclic GMP, endothelin, and PGE2 differ in preeclamptic as compared to normal pregnancies. Parameters were compared in 13 normotensive, nonpreeclamptic pregnancies, and 32 preeclamptic pregnancies. Preeclamptic women had significantly lower levels of urinary cyclic GMP (0.67 +/- 0.12 vs. 2.1 +/- 0.5 nmol/g creatinine), endothelin (0.88 +/- 0.09 vs. 3.75 +/- 1.4 ng/g creatinine), and PGE2 (26 +/- 4 vs. 9 ng/g creatinine) as compared to normals (p < 0.05). Intrarenal production of cyclic GMP, endothelin, and PGE2 are all disturbed in preeclampsia and may have implications in the sodium retention, hypertension, and intrarenal thrombosis and vasospasm of preeclamptic pregnancy.

Adult↗
PubMed1997

Increased salt retention and hypertension from non-steroidal agents in the elderly.

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.

Adult↗
PubMed1997

Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland.

The role of C-type natriuretic peptide (CNP) and its guanylyl cyclase-linked receptors in mediating salt secretion by the rectal gland of the spiny dogfish shark (Squalus acanthias) was investigated using HS-142-1, a competitive inhibitor of the binding of natriuretic peptides to their guanylyl cyclase receptors. CNP binds to receptors and activates guanylyl cyclase in rectal gland membranes in a way that is inhibited by HS-142-1. Guanylyl cyclase activation in rectal gland membranes is far more sensitive to CNP than to atrial natriuretic peptide, whereas the reverse is true for membranes derived from mammalian (rabbit) renal collecting duct cells. HS-142-1 inhibited the stimulatory effect of CNP on ouabain-inhibitable oxygen consumption by rectal gland tubules. In explanted rectal glands continuously perfused with blood from intact donor sharks, HS-142-1 inhibited the increase in salt secretion normally provoked by infusing isotonic saline solutions into the donor animal. These results strongly support the view that CNP released into the systemic circulation in response to volume expansion mediates the secretion of chloride by the rectal gland via receptors linked to guanylyl cyclase.

Adenylyl Cyclases↗
PubMed1996

Noninvasive evaluation of intrarenal oxygenation with BOLD MRI.

BACKGROUND: The countercurrent arrangement of capillary blood flow in the medulla of mammalian kidneys generates a gradient of oxygen tension between the renal cortex and the papillary tip that results in a state of relative hypoxia within the renal medulla. Exploration of the pathophysiological implications of medullary hypoxia has been hampered by the absence of a noninvasive technique to estimate intrarenal oxygenation in different zones of the kidney. In the present study, we demonstrate the feasibility of such a method on the basis of blood oxygenation level-dependent (BOLD) MRI, which allows sequential measurements in humans in response to a variety of physiological/ pharmacological stimuli in health and disease. METHODS AND RESULTS: BOLD MRI measurements were obtained in healthy young human subjects (n = 7), and the effects of three different pharmacological/physiological maneuvers that induce diuresis were studied. Spin-spin relaxation rate, R2*, was measured, which is directly related to the amount of deoxyhemoglobin in blood and in turn to tissue PO2. Furosemide but not acetazolamide (n = 6 each) increased medullary oxygenation (delta R2* = 7.62 Hz; P < .01), consistent with the separate sites of action of these diuretics in the nephron and with previous direct measurements of their effects in anesthetized rats with oxygen microelectrodes. A new finding is that water diuresis improves medullary oxygenation (delta R2* = 6.43 Hz; P < .01) in young human subjects (n = 5). CONCLUSIONS: BOLD MRI can be used to monitor changes in intrarenal oxygenation in humans in a noninvasive fashion.

Acetazolamide↗
PubMed1996

Spoiling of transverse magnetization in gradient-echo (GRE) imaging during the approach to steady state.

The signal evolution behaviors and corresponding image appearances for different methods of spoiling or refocusing the transverse magnetization in short TR gradient-echo imaging during the approach to steady state were investigated experimentally and using computer simulations based on the Bloch equations. Specifically, ideally spoiled, gradient-spoiled, gradient-refocused, and RF-spoiled pulse sequence configurations were studied. This study showed that, for the gradient-spoiled configuration, the signal evolution is position and phase-encoding order-dependent and, under typical imaging conditions, can deviate substantially from the ideally spoiled signal evolution at some spatial positions, resulting in intensity banding image artifacts. For the gradient-refocused configuration, the signal evolution oscillates toward the steady state and, generally, does not closely approximate that of ideal spoiling, resulting in different image contrast or image blurring. Using RF spoiling, the signal evolution closely approximates the ideally spoiled case for flip angles less than approximately 20 degrees and T2 values of less than approximately 200 ms and results in relatively artifact-free images. Also, this study showed that, for RF spoiling, an RF-pulse phase-difference increment other than 117 degrees, such as 84 degrees may be optimal for gradient-echo imaging during the approach to steady state.

Abdomen↗
PubMed1996

Contributions of clinical medicine to renal physiology.

The strong influence of clinical medicine on the development of renal physiology in the 20th century is a natural consequence of the striking disorders imposed by disease on the volume and composition of the fluids of the body. Clinicians well grounded in physiology were able to seize unusual opportunities provided by sick patients to elucidate principles of homeostatic control applicable to health as well as to disease. Three examples of such contributions, primarily originating at the bedside, are discussed: the role of potassium in metabolic alkalosis, the function of the parathyroid glands as exemplified by the syndrome of hyperparathyroidism, and the discovery of a humoral factor, distinct from parathyroid hormone, that may regulate phosphate excretion by the kidneys.

Clinical Medicine↗
PubMed1996

The rectal gland of Squalus acanthias: a model for the transport of chloride.

The rectal gland of the spiny dogfish shark, Squalus acanthias, secretes chloride by a furosemide sensitive process that has been termed "secondary active." Chloride enters the cell across the basolateral cell membrane via the sodium:potassium:2 chloride cotransporter. The energy for this electroneutral uptake step is provided by the electrochemical gradient for sodium directed into the cell. This is maintained by Na-K-ATPase present in the basolateral cell membrane. Present as well in the basolateral cell membrane is a potassium conductance that permits potassium to exit passively. Chloride leaves the cell across the luminal membrane via a chloride conductance closely similar to CFTR. The rectal gland is thus a model for the mechanism of secondary active chloride transport utilized by various epithelial organs throughout the vertebrate kingdom. This report reviews the humoral agents that regulate the secretion of chloride by the rectal gland and the intracellular mechanisms that mediate it. CNP, released from the heart in response to a volume stimulus, causes the release of VIP from nerves within the gland and together with VIP directly activates the rectal gland cell.

Animals↗
PubMed1996

Effect of water diuresis and water restriction on expression of HSPs-27, -60 and -70 in rat kidney.

Expression of HSP-27, HSP-60 and HSP-70 was estimated in the cortex, outer medulla and inner medulla (papilla) of rats undergoing water diuresis or water restriction for two days. The mRNAs for HSP-27 and HSP-60 in renal papilla were two- to threefold greater in rats during water restriction than in those excreting a dilute urine, but levels of mRNA for HSP-70 were not reduced by water diuresis and Western analysis for HSP-70 protein showed no difference between water-loaded and water-restricted animals.

Animals↗
PubMed1996

Myoglobinuric acute renal failure in the rat: a role for medullary hypoperfusion, hypoxia, and tubular obstruction.

Myoglobin induces renal injury by mechanisms that remain incompletely defined. In this study, the effects of myoglobin upon renal microcirculation, oxygenation, morphology, and function were investigated in anesthetized rats, and the contribution of coexisting perturbations to myoglobin nephrotoxicity were evaluated. Myoglobin infusion (3.3 mg/min) reduced outer medullary blood flow and Po2, whereas renal blood flow and cortical Po2 were unaffected. Myoglobin infusion (38 mg/100 g weight over 45 min) induced renal failure associated with collecting duct and medullary thick ascending limb dilation and casts, with focal tubular damage, confined mainly to the superficial cortex. Preconditioning with indomethacin, I-N-monomethyl arginine, and theophylline reduced cortical superficial damage but enhanced injury within the inner stripe of the outer medulla and in medullary rays, the zones of lowest O2 supply. In preconditioned animals, tubulorrhexis was primarily observed in collecting ducts transversing the inner stripe, and was remarkably reminiscent of human descriptions (J. Oliver et al., J Clin Invest 1951; 30: 1307-1440). Deterioration in kidney function closely correlated with morphologic features of both tubular obstruction and necrosis. In conclusion, medullary vasoconstriction and intrarenal hypoxia may play a role in myoglobin-induced renal failure. The deterioration in kidney function appears to reflect the combined effects of cortical damage, medullary hypoxic injury, and tubular obstruction.

Acute Kidney Injury↗