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Biomedical subjects

F S Wright

Publications and source records attributed to F S Wright.

At least 55 records · Page 3Linked to original sources
PubMed1986

Dependence of ion fluxes on fluid transport by rat proximal tubule.

The effects of changes in transepithelial water flux (Jv) on sodium, chloride, calcium, and potassium transport by the proximal convoluted tubule were examined by applying a microperfusion technique to surface segments in kidneys of anesthetized rats. Perfusion solutions were prepared with ion concentrations similar to those in fluid normally present in the later parts of the proximal tubule. Osmolality of the perfusate was adjusted with mannitol. With no mannitol in the perfusates, net fluid absorption was observed. Addition of increasing amounts of mannitol first reduced Jv to zero and then reversed net fluid flux. At the maximal rates of fluid absorption, net absorption of Na, Cl, Ca, and K was observed. When Jv was reduced to zero, Na, Cl, and Ca absorption were reduced and K entered the lumen. Na, Cl, and Ca secretion occurred in association with the highest rates of net fluid secretion. The lumen-positive transepithelial potential progressively increased as the net fluid flux was reduced to zero and then reversed. The results demonstrate that changes in net water flux can affect Na, Cl, Ca, and K transport by the proximal convoluted tubule of the rat kidney. These changes in net ion fluxes are not entirely accounted for by changes in bulk-phase transepithelial electrochemical gradients.

Animals↗
PubMed1986

Unidirectional potassium fluxes in renal distal tubule: effects of chloride and barium.

Low luminal concentrations of chloride stimulate net potassium secretion by the renal distal tubule, independent of changes in transepithelial voltage. These effects are not prevented by the luminal application of the potassium channel blocking agent barium. Because net potassium secretion comprises secretory and absorptive components, we sought to evaluate the effects of chloride and barium on unidirectional potassium fluxes in the renal distal tubule. In vivo microperfusion methods were used in anesthetized Sprague-Dawley rats. Perfusion solutions contained either 42K or 86Rb as tracers for potassium. Tracer efflux coefficients, indicating apparent potassium permeability, were similar when measured using either isotope. Net potassium flux was determined as the difference between perfusion and collected rate, and unidirectional absorptive potassium flux was calculated as the product of the mean luminal potassium concentration and the tracer efflux coefficient. During perfusion with a solution that resembled fluid normally arriving at the early distal tubule, the absorptive potassium flux was approximately 25% of the unidirectional secretory flux. Reducing lumen chloride concentration increased net potassium secretion, because blood-to-lumen potassium flux increased from 61 +/- 12.7 to 96 +/- 14.6 pmol/min. Barium reduced both absorptive and secretory fluxes but did not prevent the stimulation of net potassium secretion that occurs when luminal chloride concentration is reduced. Apparent potassium permeability during perfusion with a solution that resembled fluid normally arriving at the early distal tubule was 800 nm/s when corrected for voltage. Together with the results of previous experiments, these results are consistent with the presence of a secretory pathway linking potassium with chloride in the luminal membrane of cells of the distal tubule.

Animals↗
PubMed1986

Effects of diuretic drugs on Na, Cl, and K transport by rat renal distal tubule.

Diuretic drugs were used to characterize mechanisms involved in transporting sodium, chloride, and potassium across the wall of surface distal tubules of the rat kidney using in vivo microperfusion techniques. Both furosemide and chlorothiazide inhibited sodium and chloride absorption but did not affect the rate of potassium secretion or the transepithelial voltage. However, chlorothiazide inhibited sodium and chloride absorption more completely than furosemide and was additive to the effect of furosemide; furosemide was ineffective if chlorothiazide was already present. In contrast to the effect of furosemide, bumetanide did not affect sodium and chloride absorption but did increase potassium secretion. Amiloride reduced sodium absorption and potassium secretion without affecting net chloride absorption. These effects were additive to those of chlorothiazide. In the loop of Henle bumetanide was more effective than furosemide in inhibiting net sodium potassium and chloride absorption. It appears that cells of the distal tubule in the rat possess an Na-Cl cotransport mechanism that differs from the Na-K-2Cl cotransport mechanism found in the thick ascending limb. Sodium transport also proceeds via a conductive pathway that is inhibited by amiloride. The two modes of sodium transport, conductive and coupled to chloride, may occur in different cell types along the distal tubule.

Amiloride↗
PubMed1986

Dietary essential fatty acids, vitamin E, and Charcot-Marie-Tooth disease.

Twenty patients with type I Charcot-Marie-Tooth disease received dietary supplementation with the essential fatty acids (EFA), linoleic and gamma-linolenic acids, and vitamin E. A 3-month blinded trial of placebo (paraffin oil and vitamin E, 81.6 IU/d) was followed by 1 year of 3 grams daily of EFA and vitamin E. Serum fatty acid values doubled, but total esterified fatty acid proportions did not change. Arachidonic acid proportions correlated with the amount of prostaglandin-mediated lymphocyte suppression measured at the same times. Improvement demonstrated at the end of the placebo period by neuropsychological tests and neurologic examination was maintained during the 1 year of EFA supplementation. This effect may reflect a membrane stabilization benefit of vitamin E.

Adolescent↗
PubMed1985

Stimulation of distal potassium secretion by low lumen chloride in the presence of barium.

Potassium secretion into the renal distal tubule is increased when chloride in the tubule fluid is replaced by another anion. The present experiments were done to determine whether this increment in transported potassium traverses a conductive pathway from cell to lumen. Transport rates of potassium, sodium, chloride, and fluid by the renal distal tubule of rats were examined in vivo by continuous microperfusion. The effects of substituting gluconate for chloride in the presence and absence of 5 mM barium in the perfusion fluid were determined. When gluconate replaced chloride in the perfusion solutions, potassium secretion increased (by 44%) without a significant change in transepithelial voltage. Barium in the lumen increased the magnitude of the lumen-negative transepithelial voltage (by 30%) and reduced potassium secretion (by 56%) by inhibiting conductive potassium movement. Barium also decreased both sodium (by 51%) and chloride (by 37%) absorption. Barium did not reduce the stimulation of potassium secretion caused by reducing lumen chloride concentration. Potassium secretion increased (by 77%) when lumen chloride was reduced in the presence of 5 mM barium. We interpret these results by postulating that a cotransport mechanism linking potassium and chloride is present in the luminal membrane of distal tubule cells, that this mechanism operates in parallel with a conductive transport pathway for potassium, and that the K-Cl cotransport mechanism is not inhibited by barium.

Animals↗
PubMed1985

Dietary protein suppresses feedback control of glomerular filtration in rats.

We have examined the possibility that changes in glomerular filtration rate (GFR) after changes in dietary protein intake may depend on altered function of the tubuloglomerular (TG) feedback system. We studied male Sprague-Dawley rats after dietary pretreatment for 9.6 +/- 3.6 (SD) d with isocaloric diets containing either 6% or 40% casein. We found that GFR in rats fed the high protein diet was 24-29% higher than in rats fed the low protein diet. Simultaneous measurements of single nephron GFR (SNGFR) in the distal tubule were 6.3 nl/min or 21% higher in the rats fed the high protein diet whereas proximally measured SNGFR was not statistically different in the two groups. The higher distally measured SNGFR of rats receiving the high protein diet was associated with a 4.2 nl/min or 50% smaller suppression of SNGFR by TG feedback (-4.3 vs. -8.5 nl/min, P less than 0.001). Loop perfusion experiments demonstrated that in rats fed the high protein diet the TG feedback mechanism was less sensitive than in rats fed the low protein diet. The TG feedback response in rats fed the low protein diet, as assessed by reductions in stop-flow pressure and SNGFR, was half-maximal at flows of 14-15 nl/min. In contrast, the TG feedback response in rats fed the high protein diet was half-maximal at 22-24 nl/min. Maximal suppression of stop-flow pressure and SNGFR and the slope of the TG feedback response to increasing loop flow rates were not different in the two groups. We conclude that the sensing mechanism of the TG feedback system is rendered less responsive by a high protein intake, and that this change permits GFR to increase.

Animals↗
PubMed1985

Cerebral dysfunction after chronic hypoxia in children.

Although the long-term effects of acute anoxia have been studied, the effects of chronic hypoxia on the developing human brain have received little attention. We studied children with a cyanotic congenital heart defect to assess the impact of chronic hypoxia by eight measures: neurologic examination, visual evoked response, EEG, behavioral adjustment, cognitive, perceptual-motor, and attentional functioning, and school performance. On outcome evaluation, these children evidenced diverse neurophysiologic dysfunction. Chronic hypoxia was associated with impaired motor function, inability to sustain attention, and low academic achievement.

Brain Diseases↗
PubMed1984

Epilepsy in childhood.

The pediatrician has a central role in the diagnosis and treatment of children with epilepsy. Accurate classification of the seizure type according to the international terminology is an important step toward the selection of the most effective antiepileptic medication. Technologic advances such as CT scan, video-EEG monitoring, prolonged ambulatory EEG monitoring, and eventual clinical application of positron emission tomography have enhanced the diagnostic capabilities of both the pediatrician and neurologic specialist. Blood level monitoring of antiepileptic medication and use of basic pharmacokinetic principles have added a measure of scientific validity to the art of administration of antiepileptic medication, resulting in more effective seizure control and lessened toxicity of these drugs. The monotherapy approach to treatment has also enhanced the management of seizure disorders.

Anticonvulsants↗
PubMed1984

The effect of 2 hours of complete unilateral ureteral obstruction on tubuloglomerular feedback control.

The mechanisms affecting renal blood flow and filtration during and after unilateral ureteral obstruction (UUO) are incompletely understood. Since ureteral obstruction leads to changes in interstitial pressure and volume, and since we have previously shown that interstitial pressure conditions can modulate the sensitivity of the tubuloglomerular feedback (TGF) control system, we sought in the present study to define the contribution of the TGF system to changes in GFR during and after UUO, and to observe associated changes in pressures in vessels, tubules and the interstitial space. Interstitial pressures and glomerular filtration rate (GFR) were measured in one group of Sprague Dawley rats. Interstitial hydraulic pressure was determined with a thin catheter placed in the subcapsular space. Interstitial oncotic pressure was estimated from the protein concentration in collected hilar lymph. In a second group of rats proximal tubule pressure (PT) and stop-flow pressure (PSF) were measured during the first three hours of UUO and after 24 h UUO. In a third group of rats PSF was measured while the loop of Henle was perfused at different rates. The sensitivity of the TGF system was determined from the maximal drop in stop-flow pressure (delta PSF) and the turning point (TP)--the tubule perfusion rate at which 50% of this maximal stop-flow pressure response was obtained. In a fourth group of rats proximal tubule flow-rate was measured after release of 2 hrs UUO. The results show that PT and PSF are both increased during the first three hours of obstruction and that they return to normal or sub-normal levels after 24 h of UUO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects of luminal fluid anions on calcium transport by proximal tubule.

To determine whether the anion composition of tubule fluid affects calcium absorption by the renal proximal tubule, in vivo microperfusion techniques were employed in anesthetized rats. Experiments were designed so that total calcium and sodium concentrations were kept constant in fluids entering the tubule. A control solution, in which the main anion was chloride, was modified either by addition of ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetra-acetic acid or by replacing most of the chloride with nitrate, thiocyanate, sulfate, or citrate. Sufficient mannitol was added to the perfusion fluids to reduce net fluid flux to near zero. Net fluxes of calcium and sodium were calculated from measurements of total concentrations in perfused and collected fluids. Electrochemical driving forces across the tubule wall were calculated from measurements of transepithelial voltage and of Ca2+ activity in perfused and collected fluids. Results showed that calcium absorption by the proximal tubule depends on both the luminal Ca2+ activity and the transepithelial voltage. With zero transepithelial electrochemical driving force calcium absorption was significantly different from zero. Calcium and sodium transport rates were seen to vary independently. We conclude that the calcium absorptive mechanism involves active transport and can be dissociated from the sodium transport pathway. Calcium transport is also affected by changes in transepithelial electrochemical driving forces with an apparent permeability similar to values reported for sodium and potassium.

Animals↗
PubMed1984

Luminal influences on potassium secretion: low sodium concentration.

In vivo microperfusion techniques were employed in anesthetized rats to determine whether K secretion by renal distal tubules requires the presence of Na in luminal fluid, and, if it does, in what concentration range do changes in Na concentration have the most effect. In a first series of experiments Na in perfusion fluid was replaced at constant Cl with tetramethylammonium (TMA). When the perfusion fluid Na concentration was reduced from 96 or 34 mM to 10 or 3 mM, K secretion was reduced by 50-60% and transepithelial voltage ( VTE ) was reduced by 40-60%. In a second series of experiments, in which NaCl was replaced with urea, perfusion fluid Na concentration again was reduced to 3 mM, and K secretion and VTE were reduced. In a third series of experiments, Na was replaced with rubidium. The reduced K secretion could not be explained solely by changes in electrical driving forces. The results indicate that some luminal Na (half-maximal concentration approx 10 mM) is necessary to permit K secretion to proceed at a normal rate. Considering prior measurements of luminal Na concentration in rat distal tubules, it is unlikely that changes in luminal Na concentration play an important role in regulating the rate of distal K secretion.

Animals↗
PubMed1984

Mutual dependence of sodium and chloride absorption by renal distal tubule.

Sodium transport and chloride transport by the renal distal tubule of rats were studied by in vivo continuous microperfusion to determine the effects of separately altering luminal sodium and chloride concentrations. Results showed that sodium absorption depends on luminal sodium concentration and chloride absorption depends on luminal chloride concentration; both relations are linear between approximately 10 and 100 mM and have slopes of approximately 2.5 pmol X min-1 X mM-1. Sodium absorption is also a saturable function of luminal chloride concentration, and chloride absorption is a saturable function of luminal sodium concentration; the half-maximal chloride and sodium concentrations are approximately 10 mM. Furosemide, 10(-4) M, when added to the fluid used to perfuse this segment inhibited sodium absorption and chloride absorption to a similar extent. Removal of chloride from luminal fluid (replaced with sulfate) and addition of furosemide to the perfusion fluid had little or no effect on the measured transepithelial voltage. The results are consistent with the presence of a mechanism in the luminal membrane of distal tubule cells that couples the absorptive transport of sodium and chloride.

Absorption↗
PubMed1983

Later competence and adaptation in infants who survive severe heart defects.

A model of risk potential for developmental outcome was created based on cardiac, medical, surgical, and family-stress factors in 31 children with transposition of the great arteries who had undergone reparative open heart surgery utilizing cardiopulmonary bypass during infancy. Impact of these potential risk factors was assessed by 4 current neurologic measures (neurologic anatomic abnormalities, functional impairment, electroencephalograph [EEG], and Pattern Visual Evoked Potential [PVEP]) and 4 psychologic measures (IQ, achievement, perceptual-motor function, and behavior). Results indicated that adverse developmental outcome was significantly associated with the following medical risk variables: failure of palliative surgery to alleviate hypoxia, prolonged hypoxia, growth failure, congestive heart failure, absence of ameliorating shunting heart defects, stroke, and CNS infection; and two psychosocial moderator variables: socioeconomic status and current life stress. Analysis of a "cumulative risk score" indicated significantly higher risk scores in children with abnormal EEGs, PVEPs, and neurologic examinations. The cumulative risk score highly correlated with composite neurologic outcome (r = .62), IQ (r = -.66), achievement (r = -.60), and perceptual-motor function (r = -.48). While overall outcome was favorable for children with TGA who experienced a single risk event, outcome was compromised if multiple risk factors occurred.

Achievement↗
PubMed1982

Intraventricular hemorrhage in the full-term neonate.

Intraventricular hemorrhage (IVH) can occur in full-term newborns with a variety of clinical pictures. We studied five full-term infants who suffered IVH in the neonatal period and survived. No apparent cause for hemorrhage could be found in four. All had normal results of neurologic examinations at birth, and four had no major antecedent perinatal or postnatal difficulties. In 19 previously described full-term infants with IVH, no perinatal problems were noted in 45% of those who survived. Although more common in premature infants, IVH can occur in full-term infants and should be suspected when there is a sudden change in the neurologic status. In subsequent examinations, three of our five infants had mild spasticity and two appeared to be normal. The grading system developed for IVH in premature infants, while indicating severity of the hemorrhage, does not predict clinical outcome in full-term infants. A more definitive statement of outcome will require a longer period of observation.

Cerebral Hemorrhage↗
PubMed1982

Evidence for feedback mediated reduction of glomerular filtration rate during infusion of acetazolamide.

Systemic administration of acetazolamide (ACZ) causes glomerular filtration rate (GFR) to fall. Clearance and micropuncture experiments were done to define the mechanism of this drug effect. When rats were infused with ACZ intravenously, kidney GFR fell by 30% and single nephron (SN) GFR (measured by collecting distal tubule fluid) fell by 23%. Changes in arterial blood pressure, arterial pH, extracellular fluid volume, and proximal tubule pressure were not sufficient to account for the decrease in GFR. When SNGFR was measured by collecting proximal tubule fluid, with the loop of Henle having been blocked for 2-5 min, SNGFR was higher than the distally measured value and was not different than control. The results are consistent with the fall in GFR being caused by activation of the tubulo-glomerular feedback mechanism.

Acetazolamide↗
PubMed1982

Luminal influences on potassium secretion: chloride replacement with sulfate.

Electrolyte transport by the renal distal tubule of rats was studied by in vivo continuous microperfusion to determine whether replacing luminal chloride with sulfate would stimulate net potassium secretion. Results in a first series of experiments showed that replacing all Cl in the perfusion fluid with SO4 reduced net Na absorption, reversed the direction of net Cl transport from net absorption to net secretion, increased the lumen-negative transepithelial voltage, and increased net K secretion. In a second series of experiments adding NaCl to a perfusion fluid containing SO4 increased net Na absorption, reversed the direction of net Cl transport from net secretion to net absorption, decreased the transepithelial voltage, and decreased net K secretion. In a third series of experiments addition of 10(-6) M amiloride to a SO4-containing perfusion fluid reduced the transepithelial voltage but did not prevent the increase in K secretion, indicating that the changes in K secretion cannot be explained solely by changes in electrical driving forces. Since net fluid absorption was controlled, the changes in K secretion cannot be attributed to solvent drag effects. In all three series of experiments the rate of net K secretion was increased when luminal Cl concentration was reduced to less than 10 mM. The results suggest the existence of a cotransport system mediating K and Cl absorption by the distal tubule. Inhibition of K absorption by low lumen Cl may contribute to the increased net K secretion seen when nonchloride anions are present in distal fluid.

Animals↗
PubMed1982

Flow-dependent transport processes: filtration, absorption, secretion.

To define aspects common to different flow-dependent renal transport processes, four examples of such transport processes are considered: glomerular filtration, distal potassium secretion, ascending limb sodium absorption, and proximal fluid absorption. For each example the phenomenon of flow dependence is documented and the mechanism underlying this behavior is explored. Two general types of flow dependence are recognized: dissipative and generative. The first three processes are examples of dissipative flow dependence. In each a flow-sensitive component of the driving force for transport is generated upstream from the site of transport, the transport process tends to dissipate its driving force, and higher flow rates tend to maintain the driving force. The fourth process considered is an example of generative flow dependence. In this case the flow-sensitive component of the driving force is generated within the transporting segment. Flow affects the transport process by preventing dissipation of the driving force, as in the first three cases. Both types of processes can be expected to be more flow dependent in some lower range of flow rate and to be less flow dependent in some higher range of flow rate. This is because the proximate cause of a change in transport, a flow-dependent change in driving force is larger for a given change of flow rate when flow rates are relatively slow.

Animals↗