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Biomedical subjects

B A Stanton

Publications and source records attributed to B A Stanton.

At least 73 records · Page 4Linked to original sources
PubMed1989

Atrial natriuretic peptide inhibits a cation channel in renal inner medullary collecting duct cells.

The patch-clamp technique was used to examine the effects of atrial natriuretic peptide (ANP) and its second messenger guanosine 3',5'-monophosphate (cGMP) on an amiloride-sensitive cation channel in the apical membrane of renal inner medullary collecting duct cells. Both ANP (10(-11) M) and dibutyryl guanosine 3',5'-monophosphate (10(-4) M) inhibited the channel in cell-attached patches, and cGMP (10(-5) M) inhibited the channel in inside-out patches. The inner medullary collecting duct is the first tissue in which ANP, via its second messenger cGMP, has been shown to regulate single ion channels. The results suggest that the natriuretic action of ANP is related in part to cGMP-mediated inhibition of electrogenic Na+ absorption by the inner medullary collecting duct.

Aminoquinolines↗
PubMed1989

Renal potassium transport: morphological and functional adaptations.

Maintenance of K+ homeostasis in mammals and amphibians depends primarily on the kidneys which excrete 95% of K+ ingested in the diet. The amount of K+ in the urine is determined by the rate of K+ secretion or absorption by the distal tubule and the collecting duct. When K+ intake is increased, K+ secretion rises. The mechanisms of K+ secretion by the distal tubule and collecting duct are so efficient that K+ intake can increase 20-fold with little or no increase in body K+ content or in plasma K+ concentration. Elevated K+ secretion by the distal tubule and collecting duct occurs in part because of an increase in the quantity of Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and amplification of the basolateral membrane of principal cells. When dietary K+ intake is reduced, urinary K+ excretion falls, because K+ secretory mechanisms are suppressed and K+ absorptive mechanisms, residing in the distal tubule and collecting duct, are activated. Because a low-K+ diet is associated with hypertrophy of intercalated cells, it has been suggested that this cell type absorbs K+, possibly by an H+-K+-ATPase. In this review, I discuss the functional and morphological evidence that supports the view that principal cells secrete K+ and that intercalated cells absorb K+. In addition, some of the hormones and factors that are responsible for these changes in cell structure and function are discussed.

Adaptation, Physiological↗
PubMed1989

Characterization of apical and basolateral membrane conductances of rat inner medullary collecting duct.

Initial segments of the inner medullary collecting duct of the rat were perfused in vitro, and the electrophysiological properties of the apical and basolateral membranes were examined with KCl-filled microelectrodes. The fractional resistance of the apical membrane (FRa = Ra/Ra + Rbl) and the transepithelial resistance (RT) were estimated by cable analysis. In control tubules the transepithelial voltage (VT) averaged -2.2 mV, and the voltage across the basolateral membrane (Vbl) averaged -51.1 mV. RT was 11.9 k omega.cm (72.8 omega.cm2), and FRa was 0.94. Pretreatment of the rats with deoxycorticosterone (DOC)-pivalate for 7-10 days did not alter these electrophysiological properties. In control tubules, amiloride in the lumen (10(-5) M) changed VT from -3.0 to +1.4 mV and increased Vbl from -49.4 to -53.8 mV, RT from 12.5 to 13.6 k omega.cm, and FRa from 0.92 to 0.98. Thus the apical membrane is conductive to Na+. An increase of the bath K+ concentration from 4 to 15 mM caused an 18.8 mV depolarization of Vbl: barium in the bath also depolarized Vbl. A fivefold decrease in the [HCO3-] in the bath depolarized Vbl by 13.1 mV. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) blocked this depolarization. Thus the basolateral membrane is conductive to K+ and HCO3-. Experiments with ouabain revealed a Na+-K+-ATPase in the basolateral membrane. Taken together, the results support a model in which electrogenic Na+ absorption is driven by the Na+-K+-ATPase in the basolateral membrane, with passive movement of Na+ occurring through an amiloride-sensitive conductive pathway in the apical membrane.

Animals↗
PubMed1989

Regulation of renal ion transport and cell growth by sodium.

Intracellular sodium has been implicated in a variety of cellular processes including regulation of Na+-K+-ATPase activity, mitogen-induced cell growth, and proliferation and stimulation of Na+-K+-ATPase by aldosterone. In renal epithelial cells a rise in sodium uptake across the apical membrane increases intracellular sodium concentration, which in turn stimulates the turnover rate of Na+-K+-ATPase and thereby enhances sodium efflux across the basolateral membrane. A prolonged increase in sodium uptake causes dramatic hypertrophy and hyperplasia and a rise in the quantity of Na+-K+-ATPase in the basolateral membrane. These structural and functional changes occur in the kidney in the absence of alterations in plasma aldosterone and vasopressin levels. Several mitogens induce growth and proliferation by initiating a cascade of events, which include a rise in intracellular sodium. Accordingly, an increase in the sodium concentration within renal epithelial cells may elicit a "mitogen-like" effect by initiating the cascade at the sodium step, even in the absence of a mitogen. A rise in cell sodium may also stimulate the production of autocrine growth factors that directly or indirectly regulate cell growth and proliferation, by modifying the response to mitogens or to changes in the ionic composition of the extracellular fluid. In this review we will examine the evidence that supports a role for intracellular sodium in regulating these cellular events in renal epithelial cells.

Aldosterone↗
PubMed1989

Guanine nucleotide-binding protein, alpha i-3, directly activates a cation channel in rat renal inner medullary collecting duct cells.

We examined whether GTP binding proteins (G proteins) regulate sodium conducting channels in the apical membrane of renal inner medullary collecting duct (IMCD) cells and thereby modulate sodium absorption. Patch clamp studies were conducted on inside-out patches of the apical membrane of IMCD cells grown in primary culture. Guanosine 5'-triphosphate (GTP) and the nonhydrolyzable GTP analogue, GTP gamma S, which activate G proteins, increased the open probability of the cation channel. In contrast, the nonhydrolyzable GDP analogue, GDP beta S, which decreases G protein activity, inhibited the channel. Pertussis toxin also reduced the open probability of the channel. Addition of the alpha *i-3 subunit of Gi to the solution bathing the cytoplasmic surface of the membrane increased the open probability in a dose-dependent manner (2-200 pM). The threshold concentration for activation by alpha *i-3 was 2 pM. Activation of the cation channel by alpha *i-3 was not mediated via a protein kinase. The IMCD is the first polarized epithelium in which an ion channel has been shown to be directly regulated by a G protein. Thus, G proteins are important elements in regulating sodium absorption by the IMCD.

Animals↗
PubMed1988

A scale for the estimation of sleep problems in clinical research.

Problems in sleeping are widely prevalent in modern society and are often one of the presenting complaints of patients consulting physicians. In addition, there is scattered epidemiologic evidence and considerable clinical support that disturbed or inadequate sleep may be a risk factor for clinical emergence of cardiovascular disease and for total mortality. The role of sleep problems both as a precursor and as a sequela of disease states could be better delineated in large groups by the availability of a brief, reliable and standardized scale for sleep disturbance. Such a scale could also be used to evaluate the impact of different therapies upon sleep problems. This paper presents data from two study populations responding to three and four item self-report scales. From 9 to 12% of air traffic controllers reported various sleep problems to have occurred on half or more of the days during the prior month, whereas 12-22% of patients 6 months after cardiac surgery reported such frequent sleep problems. Utilizing data from the 6 and 12 month follow-ups, test-retest reliability of the three-item scale in cardiac surgery patients was found to be 0.59. Internal consistency coefficients for the three and four-item scales were 0.63 and 0.79 respectively.

Adult↗
PubMed1988

Electroneutral NaCl transport by distal tubule: evidence for Na+/H+-Cl-/HCO3- exchange.

The mechanisms, of electrolyte transport by isolated and perfused late distal tubules of the salamander, Amphiuma, were investigated by electrophysiological and transport techniques. The tubules absorbed Na+, HCO3-, and Cl- but not K+. The transepithelial voltage (VT) was not different from zero. Amiloride (10(-3) M) in the perfusion fluid reduced sodium absorption by 43% and HCO3- absorption by 49% without changing VT. This and previous data are consistent with the presence of a Na+/H+ antiporter in the apical membrane. Hydrochlorothiazide (HCTZ, 10(-4) M) in the perfusion fluid inhibited Na+ absorption by 48% but had no effect on HCO3- absorption or VT. Thus HCTZ reduced NaCl absorption. Intracellular microelectrode techniques were used to examine the cellular mechanisms of ion transport and sites of action of amiloride and HCTZ. Two cell types were identified by their electrophysiological properties. Neither amiloride nor HCTZ appreciably altered the electrical properties of cell type I, a cell previously identified as being involved in H+ secretion. In contrast, both diuretics hyperpolarized the basolateral membrane voltage (Vbl) of cell type II. Additional studies of cell type II showed that the removal of Cl- from the lumen hyperpolarized Vbl, as did the addition to the lumen of the Cl-/HCO3- exchange inhibitor 4,4'-diisothiocyanostilbene-2-2'-disulphonic acid. Finally, reducing the [HCO3-] of the lumen depolarized Vbl.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Amiloride-sensitive cation channel in apical membrane of inner medullary collecting duct.

Ion channels in the apical membrane of rat inner medullary collecting duct (IMCD) cells in primary culture were studied with the patch-clamp technique. A 27.5 +/- 1.2 pS non-selective cation channel was characterized in inside-out patches. The channel did not discriminate between Na+ and K+ (n = 8) and had a Na permeability-to-Cl permeability (PNa:PCl) ratio of 13:1 (n = 3). Amiloride (5 x 10(-7) M, n = 5) on the extracellular side of the membrane inhibited channel activity 10-fold at negative membrane voltages (voltage refers to cell interior with respect to patch pipette). This diuretic decreased the mean open time and increased the mean closed time without altering single-channel conductance. Voltage-dependent inhibition of this channel by amiloride distinguishes its behavior from other known nonselective cation channels. Neither voltage, Ba2+ (1 mM), tetraethylammonium (5 mM) nor changes in the bath pH (6.1 to 8.0) altered channel activity. Although the channels were active in 41% of the patches in the inside-out configuration, with a percent open time lying between 35 and 60 (-70 to +60 mV), channels were only active in 9% of the cell-attached patches. In preliminary microelectrode studies we have observed an amiloride-inhibited conductance in the apical membrane of isolated and perfused rat IMCD. Therefore, this novel nonselective cation channel identified in IMCD cells in culture may represent the amiloride-sensitive conductance observed in isolated and perfused IMCD and may mediate electrogenic Na+ absorption.

Amiloride↗
PubMed1988

Adaptation of distal tubule and collecting duct to increased sodium delivery. I. Ultrastructure.

We examined the effects of a chronic increase in tubular sodium delivery on the structure of the distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct of male Sprague-Dawley rats. Furosemide (12 mg/day) was administered by osmotic minipump for 6 days to increase the rate of sodium delivery to these segments and thereby stimulate sodium uptake. To prevent volume depletion, the furosemide-treated animals were given a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and they drank tap water. Furosemide dramatically increased urinary fluid and sodium excretion and decreased urine osmolality threefold vs. control. Furosemide treatment was associated with an increase in epithelial volume of DCT cells, CNT cells, and principal cells and an increase in the basolateral membrane area and mitochondrial volume of each cell type. These alterations in cell structure were not related to changes in plasma aldosterone, glucocorticoid, or arginine vasopressin levels. We conclude that an increase in cell sodium uptake regulates the ultrastructure of the distal tubule.

Acclimatization↗
PubMed1988

Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport.

This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.

Acclimatization↗
PubMed1987

Effects of flow rate on proximal tubule ultrastructure.

In this study we investigated the ultrastructure of the proximal tubule during alterations in fluid flow to determine whether previously observed changes in solute and water reabsorption may be related to alterations in cell ultrastructure. In each kidney, two proximal tubules (S2 segments) were perfused simultaneously at 5 and 45 nl/min. Subsequently, cell ultrastructure of control and experimental tubules was examined by electron microscopy in combination with morphometry. Changes in flow rate greatly modified the geometry of the tubule epithelium. Enhanced flow increased luminal diameter and decreased cell height. The number of microvilli per square micrometer of luminal epithelial surface area decreased with increased flow rate from a control value of 42.5 to 35.5 at high flow. However, the total number of microvilli per millimeter tubule length did not change. Thus the distance between microvilli was dependent on flow rate and was estimated to be 621, 741, and 904 A in low flow, control, and high flow tubules, respectively. We suggest that increased flow rate, perhaps by altering transepithelial hydrostatic pressure gradients, leads to an increase in the distance between the microvilli and to other alterations in cellular ultrastructure that may contribute to the augmentation of solute and water reabsorption.

Animals↗
PubMed1986

Regulation by adrenal corticosteroids of sodium and potassium transport in loop of Henle and distal tubule of rat kidney.

Studies were conducted to examine the effects of adrenalectomy (ADX) and selective, physiological adrenal corticosteroid replacement on sodium and potassium transport by the superficial loop of Henle and distal tubule of rat kidney in vivo. In the loop of Henle, ADX inhibited sodium reabsorption by 33%. Whereas dexamethasone had no effect on reabsorption, aldosterone increased sodium transport to control levels. Thus, physiological levels of mineralocorticoids, but not glucocorticoids, control a fraction of sodium reabsorption in the loop of Henle. ADX also inhibited potassium reabsorption in the loop of Henle. Both dexamethasone and aldosterone reversed the inhibition, although only aldosterone increased reabsorption to control levels. In the distal tubule, ADX reduced sodium reabsorption by 44%. Both aldosterone and dexamethasone stimulated reabsorption: however, only aldosterone increased transport to control. Potassium secretion by the distal tubule was also reduced 34% by ADX. Aldosterone, but not dexamethasone, stimulated secretion. Thus, physiological levels of aldosterone regulate a fraction of sodium reabsorption and potassium secretion in the distal tubule.

Absorption↗
PubMed1986

Clinical utility of serum digoxin level tests in hospitalized elderly patients.

To assess the clinical utility of serum digoxin tests in the elderly and to ascertain the use by physicians of test results, digoxin levels were obtained from 77 consecutive, elderly patients (means age 72 years) taking digoxin on admission to a rehabilitation hospital. Blood samples were drawn the morning following admission (prior to the administration of digoxin) and were repeated in two weeks. Signs or symptoms of digoxin toxicity were seen in all 13 patients with levels above the therapeutic range. Of 38 patients with therapeutic levels, 16 had signs or symptoms compatible with underdigitalization or digoxin toxicity. Physicians were significantly more likely to respond to both the initial and follow-up serum digoxin test result when the first test result was above the therapeutic range.

Adult↗
PubMed1985

Hospital readmissions among survivors six months after myocardial revascularization.

One neglected but important measure of early morbidity after coronary artery bypass graft (CABG) operations is rehospitalization. As part of a prospective study of recovery after elective CABG procedures conducted at four academic medical centers, data from all readmissions occurring within the first six postoperative months were collected for 326 patients. A total of 24% of patients had readmissions. The most common categories of readmission discharge diagnoses were cardiac (57%), noncardiac (26%), and surgical sequelae (17%). Factors from the initial hospitalization identified as risk factors for rehospitalization included: length of stay in intensive care unit after surgery, severe noncardiac complications, duration of preoperative cardiac symptoms, intra-aortic balloon insertion, and preoperative resting angina. These findings help to identify a subset of at risk patients for whom more careful surveillance might be beneficial.

Adult↗
PubMed1985

Structural adaptation in initial collecting tubule following reduction in renal mass.

Tubular function studies have shown that nephrectomy leads to a sharp increase in potassium secretion by initial collecting tubules. The aim of this study was to examine the relationship between potassium transport and the cellular morphology of the distal nephron. Clearance and ultrastructural studies were conducted in rats 10 days after 75% nephrectomy. Fractional urinary potassium excretion increased from 23.4 +/- 3.8% in controls to 63.9 +/- 10.1% in nephrectomized animals. Stereological analysis of principal cells in the initial collecting tubule revealed that following nephrectomy the surface density of the basolateral membrane increased from 2.32 +/- 0.12 to 4.11 +/- 0.20 micron2/micron3. While the basolateral membrane surface density of intercalated cells in this segment was not affected by nephrectomy, the luminal membrane surface density increased from 0.29 +/- 0.03 to 0.54 +/- 0.08 micron2/micron3. Ultrastructural changes were not observed in cells of the distal convoluted tubule. These observations demonstrate that cell type specific changes in membrane surface density accompany the adaptive increase in ion transport that occurs with a reduction in renal mass. The enhanced potassium excretion associated with nephrectomy may be partly mediated by a specific increase in the basolateral membrane of principal cells. The increase in luminal membrane of intercalated cells may be related to the increase in acid transport per surviving nephron following nephrectomy.

Animals↗
PubMed1985

Role of adrenal hormones in regulating distal nephron structure and ion transport.

Mineralocorticoid levels are an important determinant of membrane area and ion transport in the renal initial (ICT) and cortical (CCT) collecting tubules. Adrenalectomy leads to a dramatic and specific decrease in basolateral membrane area of principal (P) cells and depresses sodium reabsorption and potassium secretion. Although aldosterone replacement for 10 days restores basolateral membrane area and ATPase activity to control levels and dramatically elevates ion transport, glucocorticoids have no effect on basolateral membrane area, ion transport, or ATPase. It is suggested that the aldosterone-induced amplification of membrane area occurs as a mechanism whereby cells increase the number of ATPase pumps in the basolateral membrane. An acute (of 2-3 h) increase in aldosterone, but not dexamethasone, also stimulates potassium transport by the ICT. Future studies will have to establish whether the acute stimulation of transport by aldosterone involves a change in basolateral membrane area. It is concluded that mineralocorticoids, but not glucocorticoids, regulate sodium and potassium transport by P cells of the ICT and CCT, in part, by determining the number of ATPase pumps available for transport.

Adenosine Triphosphatases↗
PubMed1984

Functional benefits following coronary artery bypass graft surgery.

While some studies of patients who undergo cardiac surgery have included such outcome measures as amounts of symptom reduction and rates of resumption of employment, little attention has been focused on the extent to which these patients have experienced the simple, yet very important, broad range of functional benefits that might be anticipated by clinicians to result from operation. The present report seeks to document the extent of improvement that does exist in terms of physical, sexual, and social-role functioning. In a cohort of 340 patients (age, 32 to 69 years) studied before and six months after coronary artery bypass operation, improvements were noted in each of three dimensions of functional benefit: physical functioning (fewer total activity restrictions or incapacitated days per month), sexual functioning (through increased energy and desire and decreased pain and worry), and role functions (ability to work, social participation, and pursuit of hobbies). Further improvements might be anticipated with additional months of recovery.

Activities of Daily Living↗