Impact of the cognitive status on the memory complaints in MS patients.

OBJECTIVE: Despite the evidence of cognitive deficits in Multiple Sclerosis (MS) patients, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that these patients under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits. METHOD: Fifty-four participants (30 MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and were tested on a battery of neuropsychological tests. Based on the test results, MS patients were categorized as having either mild or moderate/severe cognitive deficits. RESULTS: The moderate/severe MS group differed from the two other groups on the Rey Auditory Verbal Learning Test (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the mild MS group did not differ from the control group on the RAVLT but did report significantly more problems than this group on the PRMQ. There was no difference between the two clinical groups on the Depression Index (Beck) but there was a significant correlation (r=.409) between the depression scores and the overestimation of prospective memory problems (PRMQ). CONCLUSION: The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable. Formal testing or information from a significant other would be advisable.

Evidence of a parathyroid hormone-independent chronic effect of estrogen on renal phosphate handling and sodium-dependent phosphate cotransporter type IIa expression.

The effects of estrogen on phosphate metabolism are not well understood. To better define the chronic effects of estrogen on phosphate balance and on renal phosphate handling, the following groups were examined: A. young male and female rats, age- and weight-matched (age 8-10 weeks, 1 (st) study), and B. ovariectomized female rats (OVX), 22 weeks old, ovariectomized aged-matched rats receiving estrogen replacement (15 micromol x 3/week) for 14 weeks (OVX+E), control female rats (intact ovaries), and male rats, both age matched to OVX and OVX+E (2 (nd) Study). In younger females (1 (st) study), plasma phosphate was lower, whereas the urinary excretion of phosphate was higher than in males. In adult intact females and in OVX+E urinary excretion of phosphate was higher than in males and OVX (2 (nd) Study). In these rats, a significant correlation between plasma phosphate and estrogen level was found. Sodium-dependent phosphate cotransporter (NaPiIIa) mRNA expression and protein abundance were higher in the renal cortex of younger male rats than in age- and weight-matched females. In adult rats, NaPiIIa mRNA and protein abundance were higher in OVX than in OVX+E, and in mature males as compared with age-matched females. These differences were not related to the parathyroid hormone (PTH) levels. Chronic estrogen administration was also associated with increased plasma calcium level and urinary calcium excretion. These results suggest that chronic estrogen treatment is associated with an inhibitory, PTH-independent effect on the expression of NaPiIIa in the kidney, leading to sex-related differences in phosphate balance.

Sensorimotor adaptation in Parkinson's disease: evidence for a dopamine dependent remapping disturbance.

Sensorimotor adaptation is thought to involve a remapping of the kinematic and kinetic parameters associated with movements performed within a changing environment. Patients with Parkinson's disease (PD) are known to be affected on this type of learning process, although the specific role of dopamine depletion in these deficits has not yet been elucidated. The present study was an attempt to clarify whether dopamine depletion in PD may directly affect the capacity to internally reorganize the visuomotor remapping of a distorted environment. Fourteen PD patients were tested twice, while they were treated and while they were withdrawn from their regular levodopa treatment. Fourteen control subjects were also enrolled and tested twice. Two parallel forms of the Computed Mirror Pointing Task (CMPT), requiring making a reaching movement in a visually transformed environment (mirror inversion), were administered to each participant. Each of them had to perform 40 trials at each of the 2 testing sessions. At each trial, sensorimotor adaptation was evaluated by the initial direction angle (IDA), which reflects the direction of movement before any visually guided readjustment. Results revealed no IDA difference at baseline, between control subject and PD patients, whether they were treated or not. In all group, IDA values at that time were large, reflecting a tendency to make movements according to the real life visuomotor mapping (based on the natural direct vision). However, striking differences appeared during sensorimotor learning, in that IDA reduction along trials was poorer in patient not treated with levodopa than both control subjects and the same PD patient treated with levodopa. No difference was observed between the treated PD patients and control subjects. Given that IDA is thought to reflect the internal representation of the visuomotor mapping, it is concluded that dopamine depletion in PD would affects sensorimotor adaptation, in that it facilitates old and poorly adapted movements (real life mapping), instead of new and more adapted ones (mirror transformed mapping).

Raclopride-induced motor consolidation impairment in primates: role of the dopamine type-2 receptor in movement chunking into integrated sequences.

Results obtained in patients with schizophrenia have shown that antipsychotic drugs may induce motor learning deficits correlated with the striatal type-2 dopamine receptors (D(2)R) occupancy. Other findings suggest that the role of the striatum in motor learning could be related to a process of "chunking" discrete movements into motor sequences. We therefore hypothesized that a D(2)R blocking substance, such as raclopride, would affect motor learning by specifically disrupting the grouping of movements into sequences. Two monkeys were first trained to perform a baseline-overlearned sequence (Seq. A) drug free. Then, a new sequence was learned (Seq. B) and the overlearned sequence was recalled OFF-drug (Seq. A recall OFF-drug). The effect of raclopride was then assessed on the learning of a third sequence (Seq. C), and on the recall of the overlearned sequence (Seq. A recall ON-drug). Results showed that performance related to the overlearned sequence remained the same in the three experimental conditions (Seq. A, Seq. A recall OFF-drug, Seq. A recall ON-drug), whether the primates received raclopride or not. On the other hand, new sequence learning was significantly affected during raclopride treatment (Seq. C), when compared with new sequence learning without the effect of any drug (Seq. B). Raclopride-induced disturbances consisted in performance fluctuations, which persisted even after many days of trials, and prevented the monkeys from reaching a stable level of performance. Further analyses also showed that these fluctuations appeared to be related to monkeys' inability to group movements into single flowing motor sequences. The results of our study suggest that dopamine is involved in the stabilization or consolidation of motor performances, and that this function would involve a chunking of movements into well-integrated sequences.

Stimulation of osteoclastic bone resorption in a model of glycerol-induced acute renal failure: evidence for a parathyroid hormone-independent mechanism.

This study was undertaken to evaluate the bone changes occurring in rats with acute renal failure (ARF). Acute renal failure was induced in rats 24 hours after dehydration by an intramuscular injection of glycerol. After induction of ARF, the rats were divided into two groups, one of which underwent parathyroidectomy (PTX). Rats with normal renal function, matched for age and weight, were used as controls and divided into two groups, one of them for PTX. At termination of the study blood and urine chemistry and bone histomorphometry were analyzed. Rats with glycerol-induced ARF developed bone changes compatible with mild hyperparathyroid bone disease, characterized mainly by increased osteoclastic bone resorption when compared with control rats having normal renal function. Rats with normal renal function following PTX developed bone disease showing complete suppression of forming and resorptive parameters. Rats with glycerol-induced ARF and PTX showed abolishment of all bone forming parameters, but a dramatic increase in osteoclastic resorption was apparent. Based on these observations we suggest that, in this model of glycerol-induced ARF, osteoclastic bone resorption may develop in the absence of parathyroid hormone, probably stimulated by other potent osteoclastogenic factors.

Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha(1)- and beta(1)-subunits in diabetic rat kidneys using RT-PCR.

The present study evaluated renal Na(+)-K(+)-ATPase activity and mRNA in rats with diabetes mellitus. To localize the segmental alpha(1)- and beta(1)-mRNAs of Na(+)-K(+)-ATPase 1 and 8 days after induction of diabetes, we used the polymerase chain reaction after reverse transcription of the mRNA in microdissected nephron segments. Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (PCT) rose on days 1 and 8 by 42 and 23%, respectively. In the medullary thick ascending limb (MTAL), it remained unchanged on day 1 and increased on day 8 by 55%. In the cortical collecting duct (CCD), activity rose by 81 and 45% on days 1 and 8, respectively. In parallel, alpha(1)-mRNA in the PCT increased by 52 and 22% on days 1 and 8, respectively. In the MTAL, alpha(1)-mRNA remained unchanged on day 1 and rose by 47% on day 8. In the CCD, alpha(1)-mRNA increased by 140 and 110% on days 1 and 8, respectively. beta(1)-mRNA was unchanged in the PCT throughout the study and was elevated in the MTAL and CCD on days 1 and 8. Thus there was a temporal dissociation between alpha(1)- and beta(1)-subunit expression. There was a highly significant linear correlation between Na(+)-K(+)-ATPase activity and alpha(1)-mRNA in all nephron segments throughout the experiment. It appears that microdissection of nephron tubules combined with reverse transcription-polymerase chain reaction defines the molecular identity of the amplified gene product and its segmental distribution in the nephron. We propose that altered gene expression may be the mechanism underlying enhanced Na(+) pump activity along the nephron in diabetic rats.

Effects of variations in food intake on renal sodium pump activity and its gene expression in Psammomys kidney.

Psammomys obesus lives in an arid environment and feeds on saltbush. When animals are fed a laboratory diet, urine osmolarity drops. To explore the mechanism(s) of water conservation, we measured renal function, kidney solute content, Na-K-ATPase activity, and mRNA in several groups: group I (saltbush diet, 18 g/day, 4.2 g protein); group II (laboratory diet, 10 g/day, 1.8 g protein); and group III, the same as group I, and group IV, the same as group II, both plus a 1-day fast. Urine osmolarity was 2,223 +/- 160, 941 +/- 144, 1,122 +/- 169 and 648 +/- 70.9 mosM in groups I, II, III, and IV, respectively. Tissue osmolarities in cortex, outer medulla, and inner medulla, respectively, were 349 +/- 14, 644 +/- 63, and 1,152 +/- 34 microosM/mg tissue in group I; 317 +/- 24, 493 +/- 17, and 766 +/- 60 microosM/mg tissue in group II; 335 +/- 6, 582 +/- 15, 707 +/- 35 microosM/mg tissue in group III; and 314 +/- 18, 490 +/- 22, and 597 +/- 29 microosM/mg tissue in group IV. There were no differences in Na-K-ATPase activity and mRNA in cortex and in medulla between groups I and II, whereas in group III Na-K-ATPase activity and mRNA increased in cortex and outer medulla. These results suggest a key role for urea in corticomedullary osmotic gradient of Psammomys. The absence of differences in Na-K-ATPase activity and mRNA between groups I and II despite differences in tissue sodium concentrations is consistent with Na-K-ATPase-independent Na absorption. Increased Na-K-ATPase activity and mRNA in fasting suggest transition to Na-K-ATPase- dependent Na transport.

Renal Na-K-ATPase hyperactivity in diabetic Psammomys obesus is related to glomerular hyperfiltration but is insulin-independent.

Psammomys obesus, a desert rodent, develops diabetes when displaced from its natural environment and fed a high energy diet in the laboratory. This study was designed to examine variations in renal function in relation to the diabetic state with emphasis on changes in Na-K-ATPase activity. The following groups of Psammomys were studied: (1) Animals fed a saltbush diet; a low energy/high salt diet (natural). (2) Animals fed a low energy/low salt diet (laboratory). Both 1 and 2 were normoglycemic and normoinsulinemic and thus served as control. (3) Animals fed a high energy diet (group C) who were hyperglycemic and hyperinsulinemic; this group was divided into two subgroups: C1 presented with glomerular hyperfiltration rate and C2 with glomerular hypofiltration rate. (4) Animals fed a high energy diet presenting with hyperglycemia-hypoinsulinemia (group D). (5) Group D+I, similar to group D but treated with external insulin (2 U/24 h). Groups D and C1, whose glomerular filtration rose above normal by 30% and 70% respectively, exhibited metabolic similarity to Type I and Type II diabetes. In these groups, Na-K-ATPase activity in the cortex increased by 80-100% and in the medulla by 180% (P<0.001 vs control). In group C2 with reduced glomerular filtration rate (GFR), Na-K-ATPase activity did not differ from control. In group D+I, with normalized glomerular filtration rate, Na-K-ATPase activity was similar to control. There was a linear and significant correlation between GFR and Na-K-ATPase activity both in the cortex and in the medulla. These experiments present a well defined animal model of diabetes mellitus. Variations in glucose and in insulin did not correlate with Na-K-ATPase activity. These results clearly demonstrated that Na-K-ATPase activity in the diabetic Psammomys was determined by glomerular filtration but was independent of plasma glucose or insulin levels.

Renal tubular Na(+)-K(+)-ATPase in diabetes mellitus: relationship to metabolic abnormality.

This study was undertaken to evaluate the effect of long-term diabetes on Na(+)-K(+)-ATPase in isolated nephron segments in five groups of rats: 1) controls of 7 wk duration (7 WD), 2) diabetes mellitus (DM) of 7 WD, 3) DM of 7 WD treated with insulin replacement, 4) DM rats of 25 WD, and 5) control rats of 25 WD. The blood glucose (BG) values in the first three groups were 123 +/- 9, 450 +/- 25, and 302 +/- 30 mg/dl; the glomerular filtration rate (GFR) was 1.34 +/- 0.08, 1.80 +/- 0.10, and 1.77 +/- 0.08 ml/min; and urinary sodium excretion was 0.94 +/- 0.05, 1.76 +/- 0.10, and 1.40 +/- 0.07 mu eq/min. Na(+)-K(+)-ATPase in group 2 increased in all segments studied (P < 0.001, group 1 vs. 2 for all). In group 3, Na(+)-K(+)-ATPase normalized in proximal convoluted (PC), proximal straight (PS), and distal convoluted (DC) tubules (P < 0.001, group 2 vs. group 3 for all), whereas in the outer medullary thick ascending limb (OMTAL) the correction was partial and in the CTAL and CCD there was no correction. In group 4 BG was 420 +/- 20 mg/100 ml compared with 123 +/- 9 in group 5 (P < 0.001), and GFR was 1.19 +/- 0.11 ml/min vs. 1.15 +/- 0.11 in group 5 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis.

1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.

Na,K-ATPase in isolated nephron segments in rats with experimental heart failure.

To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis.

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis.

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.

Effect of indomethacin in vivo and PGE2 in vitro on MTAL Na-K-ATPase of the rat kidney.

We have previously shown that prostaglandin synthesis inhibition in rats which reduces urinary excretion of PGE2 and sodium, is associated with increased Na-K-ATPase activity in renal medulla. To further characterize this interaction studies were performed in isolated segments of medullary thick ascending limb of Henle's loop (MTAL) in rats. The effect of pretreatment with indomethacin in vivo and incubation with PGE2 in vitro on MTAL Na-K-ATPase activity was studied. Pretreatment of rats with indomethacin increased Na-K-ATPase of the MTAL from 37.2 +/- 2.0 x 10(-11) mol/mm/min in controls to 62.7 +/- 2.2 (p less than 0.001) while Mg-ATPase was only slightly decreased. Incubation of MTAL Na-K-ATPase from indomethacin pretreated rats with increasing concentration of PGE2 in vitro dose dependently inhibited MTAL Na-K-ATPase activity with no effect on Mg-ATPase. Baseline Na-K-ATPase was 62.7 +/- 2.2 in MTAL from indomethacin pretreated rats and decreased to 36.9 +/- 1.4 (p less than 0.001) with 1 microM of PGE2, to 26.5 +/- 2.3 (p less than 0.001) with 10 microM PGE2 and to 22.0 +/- 1.0 (p less than 0.001) with 100 microM PGE2. 100 microM PGE2 in the incubation medium inhibited MTAL Na-K-ATPase of intact rats from 37.2 +/- 2 to 21.3 +/- 1.2 (p less than 0.001) and completely abolished the indomethacin induced increase in MTAL Na-K-ATPase. The results of this study show stimulation of MTAL Na-K-ATPase by pretreatment with indomethacin in vivo and, direct inhibition of MTAL Na-K-ATPase by PGE2 in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of thick ascending limb Na+-K+-ATPase activity in salt-loaded rats by furosemide.

To evaluate the role of increased thick ascending limb Na+-K+-ATPase activity in rats undergoing hypertonic salt loading, the following groups of rats were studied: 1) control rats, 2) rats receiving an oral hypertonic Na load for 7 days, and 3) rats receiving the same oral Na load as in group 2 plus a daily injection of 10 mg/100 g of furosemide ip for 7 days. Salt loading (group 2) was associated with increased glomerular filtration rate (GFR) and hence an increased filtered load of sodium. Plasma aldosterone levels were markedly decreased. Na+-K+-ATPase was unchanged in the proximal tubule [convoluted (PC) and straight (PS)], increased in the thick ascending limb of Henle's loop [outer medullary (OMTAL) and cortical (CTAL)] and decreased in the distal nephron [distal convoluted tubule (DCT) and cortical collecting duct (CCD)]. The renal corticomedullary gradient of solutes was markedly increased in the salt-loaded group. Salt loading plus furosemide for 7 days (group 3) was associated with severe dehydration and hypernatremia. GFR as well as plasma aldosterone levels were unchanged compared with control. Na+-K+-ATPase was significantly increased in the proximal tubule (PC and PS), markedly decreased in the thick ascending limb of Henle's loop (OMTAL and CTAL), increased in the DCT and unchanged in the CCD. The increase in the corticomedullary gradient caused by salt loading per se was abolished by treatment of salt-loaded rats with furosemide. These results indicate that treatment with furosemide prevents the preservation of water balance and of normal body fluid tonicity in rats undergoing hypertonic Na loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced glomerular filtration and Na+-K+-ATPase with furosemide administration.

To evaluate the effect of furosemide on kidney function, glomerular filtration rate (GFR), urinary Na excretion (UNaV), Na reabsorption (NAR), and Na+-K+-ATPase in isolated nephron segments were measured in 1) rats treated with furosemide 10 mg X 100 g-1 X 24 h-1 ip for 7 days, and 2) rats receiving an oral Na load for 12 days. In furosemide-treated rats, GFR rose from 0.61 +/- 0.03 (mean +/- SD) to 0.83 +/- 0.06 ml/min (P less than 0.01), UNaV rose from 904 +/- 71 to 1,402 +/- 85 mueq/day (P less than 0.001), and net NAR rose from 87.5 +/- 3.7 to 116.7 +/- 9.0 mueq/min (P less than 0.01). Na+-K+-ATPase remained unchanged in the proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical thick ascending limb of Henle's loop (cTALH), and medullary thick ascending limb of Henle's loop (mTALH), but was increased in the distal convoluted tubule (DCT) and in cortical collecting duct (CCD) from 48.5 +/- 1.2 to 75.3 +/- 0.7 (P less than 0.001) and from 18.6 +/- 0.7 to 27.1 +/- 2.7 (P less than 0.02) X 10(-11) mol X mm-1 X min-1, respectively. In Na-loaded rats GFR rose from 0.61 +/- 0.04 to 0.86 +/- 0.03 ml/min (P less than 0.001), UNaV rose from 1,064 +/- 118 to 18,532 +/- 2,045 mueq/day (P less than 0.001), net NAR from 88.1 +/- 3.0 to 107.8 +/- 3.9 mueq/min and Na-K-ATPase in the mTALH rose from 40.3 +/- 1.4 to 56.2 +/- 2.11 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced renal tubular ouabain-sensitive ATPase in streptozotocin diabetes mellitus.

The effect of streptozotocin-induced diabetes mellitus on rat renal ouabain-sensitive ATPase in six distinct nephron segments was studied. Twenty-four hours after administration of streptozotocin, blood glucose increased threefold (P less than 0.001), and glucosuria was evident. Aldosterone levels increased almost twofold (P less than 0.001). Ouabain-sensitive ATPase increased in the proximal segments PC (proximal convoluted tubule) and PS (proximal straight tubule) by 43 and 62%, respectively, (P less than 0.001) and CD (cortical collecting duct) ouabain-sensitive ATPase increased 77% (P less than 0.001). Ouabain-sensitive ATPase in the cortical (CTAL) and medullary (MTAL) thick ascending limbs of Henle's loop and in the DC (distal convoluted tubule) remained unchanged after 24 h of streptozotocin administration. Eight days after streptozotocin administration, when glomerular filtration rate (GFR) was already markedly elevated, ouabain-sensitive ATPase remained increased in the PC, PS, and CD but was significantly less compared with the activity after 24 h (P less than 0.05), whereas in the CTAL and MTAL a marked increase in ouabain-sensitive ATPase occurred by 54% in the CTAL and 65% in the MTAL (P less than 0.001). Aldosterone levels remained elevated compared with control but less than after 24 h. Pretreatment with deoxycorticosterone acetate abolished the increase in ouabain-sensitive ATPase in the CD. These findings show that streptozotocin-induced diabetes mellitus in the rat is associated with a substantial increase in ouabain-sensitive ATPase activity along most of the nephron. This increase in enzyme activity may represent a mechanism of physiological adaptation of the nephron to maintain electrolyte homeostasis in diabetes in face of the increased GFR and osmotic diuresis.

Parallel changes in red blood cell and renal Na-K-ATPase activity in adrenal and electrolyte disorders in the rat.

To compare the activity of Na-K-ATPase in the red blood cells (RBCs) and in renal tissue in disorders of Na+ metabolism, the following groups of rats were studied: 1) control, intact rats, 2) adrenalectomized (ADX) rats, 3) intact rats treated with DOCA, 4) ADX DOCA-treated rats, 5) intact salt-loaded rats, 6) ADX salt-loaded rats, 7) intact dexamethasone-treated rats (DEXA), and 8) ADX DEXA-treated rats. After adrenalectomy (group 2) serum Na+ decreased and serum K+ increased. Renal Na-K-ATPase in cortex, medulla and papilla of the control group was 44 +/- 2.7 mumol Pi/mg prot/h, 128.2 +/- 5.9 and 44 +/- 3.2 respectively and in group 2 the enzyme activity was 32.5 +/- 2.0 (P less than 0.005), 81.7 +/- 4.5 (P less than 0.001) and 23.6 +/- 1.9 (P less than 0.001) respectively. RBCs Na-K-ATPase of control animals was 2.82 +/- 0.19 mumol Pi/mg prot/h, while in group 2 the activity was 1.43 +/- 0.24 (P less than 0.001). DOCA treatment of ADX rats (group 4) normalized serum electrolytes and Na-K-ATPase activity in the renal cortex and papilla and in the RBCs. In the renal medulla the correction by DOCA was only partial. Salt loading of ADX rats (group 6) normalized serum electrolytes and Na-K-ATPase activity in the renal medulla and RBCs. Salt loading of normal rats increased RBC Na-K-ATPase to 3.72 +/- 0.36 (P less than 0.02) and medullary Na-K-ATPase to 185.6 +/- 9.8 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Na-K-ATPase in isolated rabbit tubules after unilateral nephrectomy and Na+ loading.

Na-K-ATPase activity was studied in tubule segments from the cortex and medulla of rabbit kidneys under normal conditions, after unilateral nephrectomy, and after chronic salt loading. After unilateral nephrectomy kidney weight increased by 37% and Na-K-ATPase activity rose significantly in all nephron segments by 36-200% (P less than 0.01). Oral salt loading for 2 wk with 0.5% NaCl caused an increase in GFR and in absolute sodium excretion as well as reabsorption; plasma aldosterone decreased by 44% (P less than 0.005). In the proximal segments (PCT, CPST, OMPST, and TDL) there were no marked changes in Na-K-ATPase activity, whereas along the whole length of the ascending limb of Henle's loop (iMTAL, MTAL, and CTAL) there was a significant rise in the enzymatic activity of 30-200% (P less than 0.02). In the distal segments (DCT, CCD, and OMCD) there was a marked decrease of 50-60% (P less than 0.005) in Na-K-ATPase activity after the salt loading. We conclude that unilateral nephrectomy caused a general increase in Na-K-ATPase activity along the whole length of the nephron, and salt loading caused a selective increase in enzyme activity along the ascending limb of Henle's loop and decrease in the distal segments.