Decreased Ouabain-Sensitive Adenosine Triphosphatase Activity in the Erythrocyte Membrane of Patients with Chronic Renal Disease

Cole, C.

doi:10.1042/cs0450775

Cited by 59 publications

(48 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data for this patient were not included in the statistical analysis as he was found to be an outlyer by using the BMDP statistical software package. 13 …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Khalil-Manesh¹,

Venkataraman²,

Samant³

et al. 1987

Hypertension

View full text Add to dashboard Cite

SUMMARY The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na + ,K + -adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 ± 8.9; drug-treated, 86.9 ± 4.9 mm Hg; p<0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 ± 1.8; drug-treated, 5.2 ± 0.4 mmol/L cells; p<0.002) and calcium (placebo, 13.5 ± 1.6; drug-treated 10.8 ± 3.3 Mmol/L cells; p<0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+ ,K + -ATPase of erythrocyte membranes (placebo, 7.1 ± 1.1 x 10-J ; drug-treated, 9.0 ± 0.6 x 10-2 fiM inorganic pbosphate/hr/mg; p < 0.001) at the end of the study. However, no significant change in the ouabaininsensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx. It is concluded that diltiazem reduces diastolic blood pressure of hypertensive subjects. Erythrocyte studies indicate that diltiazem not only blocks entrance of calcium into the cells but may also stimulate Na+,K+-ATPase activity, resulting in reduction in intracellular sodium concentration, thus suggesting a possible dual mechanism for its antihypertensive effects. 18In the present investigation, we studied the changes that occur in the erythrocytes of hypertensive persons treated with diltiazem to test the hypothesis that the abnormalities in the red blood cell cation concentrations and various pump activities are reversed in those who respond to the drug treatment. These studies were conducted in a placebo-controlled, double-blind, parallel fashion. Patients and Methods Selection of Study PatientsThe protocol was approved by the institutional review board, and written informed consent was obtained from each subject. Twenty-one patients, 12 men (average age, 51 ± 15 years) and 9 women (average age, 57 ± 13 years), completed the protocol. Inclusion criteria were 1) a stable resting supine diastolic blood pressure (DBP) between 95 and 110 mm Hg at least 2 weeks after cessation of antihypertensive medications and 2) a stable DBP with variation of 7 mm Hg or less 19between two consecutive weekly measurements starting with days 7 through 10 of the placebo run-in.After a 2-week placebo run-in phase, the eligible patients were randomized to placebo...

show abstract

“…The data for this patient were not included in the statistical analysis as he was found to be an outlyer by using the BMDP statistical software package. 13 …”

Section: Resultsmentioning

confidence: 99%

“…The ATPase activity was assayed 13 in a medium containing 0.3 to 0.5 mg of erythrocyte per milliliter, 50 mM Tris (pH 7.4 at 37°Q, 6 mM MgCl ? , 100 mM NaCl, 20 mM KC1, 6 mM adenosine 5'-triphosphate (ATP) and 0.5 mM EGTA and a medium containing the same components plus 0.2 mM ouabain.…”

Section: Measurement Of Na+k + -Atpase Of Erythrocytesmentioning

confidence: 99%

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Khalil-Manesh¹,

Venkataraman²,

Samant³

et al. 1987

Hypertension

View full text Add to dashboard Cite

show abstract

“…In Table 2 (Wilkinson, 1975) (Welt, Smith, Dunn, Czerwenski, Proctor, Cole, Balfe & Gitelman, 1967;Cole, Balfe & Welt, 1968;Cole, 1973). They have found that the plasma of uremic patients contains a dialysable substance which inhibits Na +-K +-ATPase activity in normal human erythrocytes but that this inhibition occurs predominantly when the plasma is that of uremic patients with high intraerythrocytic sodium concentrations (Cole et aL, 1968).…”

Section: Discussionmentioning

confidence: 99%

Altered Distribution of Digoxin in Renal Failure—a Cause of Digoxin Toxicity?

Aronson¹,

Grahame‐Smith²

1976

Brit J Clinical Pharma

View full text Add to dashboard Cite

1Three cases are described in which renal failure was accompanied by a lowered apparent volume of distribution of digoxin. In two cases this resulted in frank digoxin toxicity and in one equivocal toxicity. In all three cases digoxin plasma levels were greater than 2 ng/ml. 2 The possible causes of the abnormal distribution of digoxin in renal failure are discussed. 3 Recommendations are outlined for the use of digoxin in patients with renal failure aimed at circumventing the problem raised by a lowered apparent volume of distribution of the drug.

show abstract

“…An increase in intracellular Na was first described in erythrocytes from some patients with chronic renal failure some two decades ago (5). Subsequently, several groups of investigators have provided evidence for a defect in Na transport of erythrocytes (6)(7)(8)(9), leukocytes (10), and skeletal muscle ( 11) from uremic subjects.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier efforts to explore the mechanism of the rise in intracellular Na were limited to measurements of pumpmediated Na efflux, the passive Na leak, and Na-K-ATPase activity (5)(6)(7)(8)(9)(10)(11)(12). In the present study, the number of Na-K pump sites was quantitated by the technique of [3H]ouabain binding (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of alteration of sodium potassium pump of erythrocytes from patients with chronic renal failure.

Cheng¹,

Kahn²,

Kaji³

1984

J. Clin. Invest.

View full text Add to dashboard Cite

substantial increase in cell Na, K pump influx was not higher in uremic erythrocytes with high cell Na. When intracellular Na was altered with nystatin (cell Na equal to 120 mmol/liter cell water in both groups), K pump influx was proportional to the number of Na-K pump sites so that the ion turnover rate per pump site was similar in the two groups. Uremic plasma failed to depress K pump influx of normal erythrocytes. The passive net influx of Na in uremic cells with high intracellular Na was not different from that observed in erythrocytes from normal subjects. When erythrocytes were separated by age on Percoll density gradients, the number of Na-K pump sites of the youngest uremic Preliminary reports of this work were presented at

show abstract

Decreased Ouabain-Sensitive Adenosine Triphosphatase Activity in the Erythrocyte Membrane of Patients with Chronic Renal Disease

Cited by 59 publications

References 8 publications

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Altered Distribution of Digoxin in Renal Failure—a Cause of Digoxin Toxicity?

Mechanism of alteration of sodium potassium pump of erythrocytes from patients with chronic renal failure.

Contact Info

Product

Resources

About