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Biomedical subjects

S K Mujais

Publications and source records attributed to S K Mujais.

At least 37 records · Page 2Linked to original sources
PubMed1993

Potassium adaptation in hypothyroidism: changes in transport adenosinetriphosphatases.

To evaluate whether hypothyroidism alters the adaptive responses of renal transport adenosine-triphosphatases (ATPases) to modifications in dietary K content, we examined the activities of Na-K pump and H-K pump in hypothyroid rats under basal conditions and after dietary K changes. Hypothyroidism led to a decline in Na-K pump activity in all three nephron segments examined [proximal convoluted tubule from 2,333 +/- 103 to 1,099 +/- 32, medullary thick ascending limb from 4,344 +/- 119 to 1,613 +/- 61, and cortical collecting tubule (CCT) from 1,133 +/- 45 to 640 +/- 38 pmol.mm-1 x h-1; all P < 0.01 vs. euthyroid] along with morphological changes manifest in a decrease in tubule diameter. K loading led to an increase in Na-K pump activity in the CCT of both euthyroid (from 1,133 +/- 45 to 2,269 +/- 74, pmol.mm-1 x h-1, P < 0.01) and hypothyroid (from 640 +/- 38 to 1,118 +/- 67 pmol.mm-1 x h-1, P < 0.01) animals. Furthermore, in euthyroid rats, 3 wk of K depletion led to a major increase in H-K pump activity in both the CCT (from 203 +/- 14 to 331 +/- 22 pmol.mm-1 x h-1, P < 0.01) and medullary collecting tubule (MCT, from 137 +/- 9 to 210 +/- 14 pmol.mm-1 x h-1, P < 0.01). Hypothyroidism was associated with a decline in H-K pump activity in the CCT and MCT (to 94 +/- 6 and 55 +/- 5 pmol.mm-1 x h-1, respectively; both P < 0.01 vs. euthyroid).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Regulation of the renal Na:K pump: role of progesterone.

In male Sprague-Dawley rats, the effects of exogenous high physiologic levels of progesterone simulating those observed in pregnancy (5 mg/day) on Na:K pump activity (picomoles per millimeter per hour) in microdissected nephron segments were evaluated. In adrenal-intact rats, progesterone led to a generalized decrease in Na:K pump activity in proximal convoluted tubule from 2,524 +/- 61 to 741 +/- 41 (71% reduction; P < 0.01), medullary thick ascending limb (MAL) from 4,793 +/- 217 to 2,000 +/- 133 (59% reduction; P < 0.01), and cortical collecting tubule (CCT) from 1,141 +/- 69 to 591 +/- 133 (49% reduction; P < 0.01). This effect was similar in magnitude to the decline observed with adrenalectomy alone. In adrenalectomized rats, progesterone had no further inhibitory effect on the pump in MAL (2,172 +/- 66 versus 2,312 +/- 71) or CCT (493 +/- 58 versus 530 +/- 31) but led to a modest decline in Na:K pump activity in the proximal convoluted tubule (from 1,136 +/- 88 to 528 +/- 31; P < 0.01). In adrenal-intact rats, a high K diet for 7 days led to an increase in CCT Na:K pump activity from 1,141 +/- 69 on a normal potassium diet to 2,224 +/- 33 pmol/mm per h (P < 0.001). Progesterone treatment reduced basal Na:K pump activity in CCT, and concurrent progesterone treatment blunted the stimulatory effect of K adaptation on the pump (973 +/- 68 pmol/mm per h; P < 0.001 versus untreated).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1993

Maleic acid-induced proximal tubulopathy: Na:K pump inhibition.

Maleic acid (MA) administration to experimental animals induces a rapid, reversible, complex dysfunction of the renal tubule resembling Fanconi's syndrome. The intent of this work was to characterize the changes in the Na:K pump along the nephron during the development and recovery from MA injury to better define the site of damage and to correlate the observed changes in Na:K pump function with alterations in metabolic function. Male Sprague Dawley rats were studied before and 2 and 24 h after the injection of MA (100 mg/kg iv). MA induced an early and reversible decline in Na:K pump activity in the proximal convoluted tubule (PCT) from 2,324 +/- 61 to 1,446 +/- 55 pmol/mm.h (P < 0.001). This decrement was transient because enzyme activity returned to near baseline by 24 h after MA administration. The changes in Na:K pump activity were restricted to the PCT because no change in pars rectae, in medullary thick ascending limb, or in medullary collecting tubules was observed. PCT obtained from MA-treated rats 2 h after drug injection showed a decline in 14CO2 formation from radiolabeled glutamine, implying impaired oxidation of the carbon skeleton of the amino acid. This decline was transient with recovery of oxidative rates to normal 24 h after MA administration. It was concluded that a reversible, segment-specific impairment in PCT Na:K pump occurs early after the administration of MA. The decline in PCT Na:K pump activity is paralleled by a decrement in oxidative metabolism and may underlie the many consequences of this model of proximal tubulopathy that are reflections of impairment in sodium-dependent transport processes.

Adenosine Triphosphatases↗
PubMed1992

Renal handling of enalaprilat.

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.

Adult↗
PubMed1992

Uremic pancreopathy: impaired secretory function in vitro.

Abnormalities of the exocrine pancreas have long been described in uremia. The present study was performed to determine whether these abnormalities occur as a result of derangements in protein synthesis or disturbances in protein secretion. Pancreatic acini obtained from rats with renal failure and their pair-fed shams were studied in vitro by the method of radiolabeled leucine incorporation and secretory response to carbachol. In vitro protein synthesis, as reflected in radiolabeled leucine incorporation per DNA content was increased in uremic acini compared with control. However, the secretory response to carbachol was impaired. These results suggest that the impairment in exocrine pancreatic function is likely due to abnormalities in protein secretion, rather than protein synthesis.

Animals↗
PubMed1992

Discordant aspects of aldosterone resistance in potassium depletion.

Aldosterone resistance, defined as absent kaliuretic response to exogenous hormone, has been described in K depletion. It is not clear whether the absent kaliuresis is due to activation of K-conserving mechanisms or to failure of activation of the Na-K pump in cortical collecting tubules (CCT) by mineralocorticoids. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal or low-K diet. Na-K pump activity (pmol.mm-1.h-1) in microdissected CCT and medullary collecting tubules (MCT, inner stripe of the outer medulla) was determined at 7 or 21 days after allocation to the dietary groups before and after exogenous aldosterone (50 micrograms twice daily, for 3 days). K depletion led to progressive hypertrophic changes in the CCT and MCT manifest in an increase in basal Na-K pump activity. In both K repletion and short-term K depletion (7 days), aldosterone led to the expected increase in CCT Na-K pump activity. With long-term K depletion, the CCT Na-K pump response to aldosterone was blunted. In the MCT where under normal conditions the Na-K pump is aldosterone unresponsive, an increasing aberrant responsiveness to the mineralocorticoid was observed with progressive K depletion. We conclude that apparent aldosterone resistance in short-term K depletion is likely due to activation of K-conserving mechanisms with early preservation of the CCT biochemical response to the hormone. With long-term K depletion, a blunted biochemical response to aldosterone may contribute to the absent kaliuretic response. In the MCT, K depletion led to the development of aberrant responsiveness to aldosterone.

Adenosine Triphosphatases↗
PubMed1992

Vasopressin resistance in potassium depletion: role of Na-K pump.

Resistance to the hydrosmotic effects of vasopressin has been described in K depletion. It is not clear whether other effects of vasopressin, notably its effects on the Na-K pump in the collecting duct, are similarly affected. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal K (NK) or low-K (LK) diet. Na-K pump activity (pmol.mm-1.h-1) in cortical collecting duct (CCD) and medullary collecting duct (MCD) was determined at 21 days after allocation to the dietary groups before and after exogenous vasopressin (0.1 U twice daily for 3 days). In animals on NK diet, vasopressin (AVP) led to a doubling of Na-K pump activity in the CCD from 502 +/- 47 to 1,144 +/- 41 pmol.mm-1.h-1 (P < 0.01). In K-depleted animals, which had a higher baseline Na-K pump activity, an increase was also observed from 1,056 +/- 97 to 1,239 +/- 65 pmol.mm-1.h-1 (P < 0.05), but this increase was quantitatively less, with the change being 183 vs. 642 pmol.mm-1.h-1 in K-replete rats. The findings in the MCD were similar; in rats on a NK diet, AVP led to a significant increase in Na-K pump activity from 498 +/- 29 to 830 +/- 28 pmol.mm-1.h-1 (P < 0.01). With K depletion, this directional change was preserved, increasing from 1,380 +/- 49 to 1,556 +/- 45 pmol.mm-1.h-1 (P < 0.05), but was quantitatively less than in K-replete rats, the change being 176 vs. 332 pmol.mm-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1992

Gaps in the anion gap.

OBJECTIVE: To review limitations of the use of serum anion gap in clinical practice. DATA SOURCES: Original reports and reviews. STUDY SELECTION: Sources containing the most recent pertinent information. DATA SYNTHESIS: Theoretical and practical limitations beset the use of serum anion gap. Awareness of these limitations reduces but does not eliminate wrong diagnoses based on the anion gaps. CONCLUSIONS: Serum anion gap has a limited value in the differential diagnosis of acid-base disorders and can be misleading.

Acid-Base Equilibrium↗
PubMed1990

Cortical collecting duct Na-K pump in obstructive nephropathy.

The present study examined the alterations in the cortical collecting tubule (CCT) Na-K pump that occur after unilateral ureteral obstruction and their consequences on electrolyte excretion. In male Sprague-Dawley rats, unilateral ureteral ligation led to a progressive decrease in intact CCT Na-K pump in situ turnover worsening with the duration of the obstruction: control, 20.1 +/- 0.4; obstructed kidney: 3 h, 14.6 +/- 0.3; 12 h, 12.7 +/- 0.6; 24 h, 12.8 +/- 0.5; 48 h, 11.6 +/- 0.5; and 96 h, 10.6 +/- 0.4 pmol Rb.mm-1.min-1 (all P less than 0.001 vs. control). CCT diameter increased with the duration of obstruction. Release of ureteral obstruction was associated with restitution of pump turnover rate. With 3 h of obstruction, recovery of pump in situ turnover was complete (19.7 +/- 0.4 pmol Rb.mm-1.min-1) by 24 h after release. With more prolonged obstruction (24 h) recovery was partial by 24 h postrelease (16.2 +/- 0.5 pmol Rb.mm-1.min-1) and complete (19.8 +/- 0.7 pmol Rb.mm-1.min-1) by 48 h, suggesting a delay in recovery without the occurrence of irreversible damage. The impairment in Na-K pump in situ turnover was paralleled by an impairment in the ability of the obstructed kidney to excrete an acute potassium load. This parallelism of functional and biochemical studies favors the notion that impairment of CCT Na-K pump in situ turnover contributes significantly to the abnormal potassium excretion that accompanies obstructive damage.

Animals↗
PubMed1989

Gentamicin nephrotoxicity in extrahepatic cholestasis: modulation by dietary calcium.

The present study was designed to test the hypothesis that the presence of a specific hepatobiliary disease, namely common bile duct obstruction, in the absence of other risk factors will exacerbate gentamicin nephrotoxicity. Furthermore, since bile duct ligation decreases urinary calcium excretion, we studied the role of calcium supplementation in the prevention of gentamicin nephrotoxicity in this model. Male Sprague-Dawley rats were allocated to sham groups and common bile duct ligation groups. Gentamicin at 40 and 100 mg per kg per day for 5 days induced a more severe azotemia in common bile duct ligation animals than in sham controls. Furthermore, higher levels of renal gentamicin were found in common bile duct ligation rats than in sham rats early in the course of therapy, at its termination and during the recovery period. Pretreatment of common bile duct ligation animals with dietary calcium supplementation significantly attenuated gentamicin nephrotoxicity and the increased renal gentamicin accumulation, whereas initiation of calcium supplementation concurrent with gentamicin administration had no salutary effect. We conclude that experimental extrahepatic cholestasis in the rat, in the absence of any other factor, potentiates gentamicin nephrotoxicity. The effect is prevented by pretreatment with dietary calcium supplementation but is not modified by concurrent administration of a high-calcium diet.

Animals↗
PubMed1989

Stimulation of erythrocyte and renal Na+,K+-adenosine triphosphatase activity by antidigoxin antibody in normal rats.

1. A circulating ouabain-like factor which inhibits the Na+,K(+)-pump has been implicated in volume-expanded states. To assess the role of this putative factor in normovolaemic rats, we measured erythrocyte and renal Na+,K(+)-adenosine triphosphatase activity after the infusion of a mixture of high-affinity digoxin-binding Fab fragments (Digibind) capable of removing digoxin from pump sites. 2. Compared with either saline (vehicle) or sheep immunoglobin G, infusion of the antidigoxin antibody caused a moderate increase of Na+,K(+)-adenosine triphosphatase activity in the erythrocyte (saline 348 +/- 12; immunoglobulin G 339 +/- 16; antidigoxin antibody 432 +/- 22 nmol h-1 mg-1; P less than 0.005 by analysis of variance) and a larger increase in the renal cortex (saline 9.7 +/- 0.9; immunoglobulin G 9 +/- 1.4; antidigoxin antibody 24.3 +/- 1.8 mumol h-1 mg-1; P less than 0.0005 by analysis of variance) without a change in blood pressure. 3. These results are consistent with the presence of a digoxin-like inhibitor of the Na+,K+-pump in normal rats.

Animals↗
PubMed1989

Renal potassium adaptation: role of the Na+-K+ pump in rat cortical collecting tubules.

To evaluate the mechanism of renal potassium adaptation we explored several facets of Na+-K+-ATPase function during K loading in rat cortical collecting tubule (CCT). Urinary K excretion increased within the 1st day after initiation of dietary loading to a level matching intake, indicating the early onset of K adaptation. CCT Na+-K+-ATPase activity after 1 and 2 days on the high-K diet was not different from that observed in control animals, whereas it increased to threefold base line after 7 days. Similarly, the specific binding of ouabain was unchanged by 2 days of high-K diet, but was increased on the 7th day. In contrast, there was an early increase in Rb uptake that persisted throughout the period of observation. Acute (60 min) KCl infusion into control rats led to a significant increase in Rb uptake, whereas Na+-K+-ATPase hydrolytic activity remained unchanged. In the isolated perfused kidney, increasing perfusate K led to an increase in CCT Rb uptake similar to that observed in vivo, again without altering the hydrolytic activity of the enzyme. We conclude that K adaptation is an early event developing rapidly after initiation of dietary change. In its early phase the Na+-K+ pump responds by increasing K-transport rate to accommodate the acute homeostatic need; when the requirement for increased K secretion is sustained, a different adaptive pattern emerges characterized by an increase in the number of pumps. The adaptive response to an acute K load appears to be an intrinsic property of the pump independent of hormonal influences.

Acclimatization↗
PubMed1988

Renal memory after potassium adaptation: role of Na+-K+-ATPase.

The present study was designed to explore the time course of the resolution of enhanced Na+-K+-ATPase activity in the cortical collecting tubule (CCT) and the parallel changes in renal K excretion that are characteristic of potassium adaptation. Potassium-adapted male Sprague-Dawley rats manifested an enhanced kaliuretic response to an acute intravenous load of KCl and a doubling of Na+-K+-ATPase activity in the CCT. Withdrawal of dietary K loading from these adapted rats was associated with a gradual resolution of these adaptive biochemical (t1/2 of Na+-K+-ATPase return to base line 48 h) and excretory changes. During this resolution phase, however, a temporal discrepancy was uncovered between the change in dietary K and the slower changes in enzyme activity and renal K excretion with a persistence of the enhanced kaliuresis leading to a negative K balance. We conclude that the slow inactivation, after withdrawal of K loading, of the increased membrane transport proteins of K adaptation, will manifest as a renal memory of the antecedent excretory requirements.

Acclimatization↗