Stimulation of K+ fluxes by diuretic drugs in human red cells

Garay, Ricardo P.; Nazaret, Corinne; Dı́ez, Javier; Etienne, A.; Bourgain, R.H.; Braquet, P.; Esanu, André

doi:10.1016/0006-2952(84)90567-7

Cited by 71 publications

(29 citation statements)

References 12 publications

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“…3 Several transport mechanisms, including the Na + -K + pump, 4 Na + -Li + countertransport, 5 and Na + -K + cotransport, 6 have been implicated in the pathogenesis of hypertension. In the erythrocyte, these transport systems have been suggested to be qualitatively similar to those in the kidney, 7 and their easy accessibility has enabled their study.…”

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confidence: 99%

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

et al. 1988

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SUMMARY Sodium transport of erythrocytes from normotensive and essential hypertensive subjects was evaluated by determining ouabain-sensitive and ouabain-insensitlve sodium efflux rates, Na + -LI + countertransport rates, Li + -K + cotransport rate constants flithium replacing sodium), intracellular sodium concentrations, and the number of Na + ,K + -adeoosine triphosphatase (ATPase) sites per erythrocyte. Subjects included men and women, blacks and whites. Hypertensive subjects had significantly higher sodium transport than did normotensive subjects for ouabain-sensitive sodium efflux (p < 0.025) and Na + -Li + countertransport (p < 0.001). Sexual differences were noted for ouabain-sensitive (p < 0.001) and ouabain-insensitive (p < 0.001) sodium efflux, for Intracellular sodium concentration (p < 0.025), and for the Li + -K + cotransport rate constant (p < 0.005), all with higher values for men than for women. Racial differences were noted for ouabaln-lnsensitive sodium efflux (p < 0.005), Na + -Li + countertransport (p < 0.001), and the Li + -K + cotransport rate constant T HE relationship between dietary sodium intake and blood pressure has long been recognized. 1 We now know that heterogeneity of blood pressure response to sodium exists in normotensive and hypertensive subjects.2 Sodiumsensitive persons may also have an abnormality in the ability of their kidney to excrete a sodium load.

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confidence: 99%

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

et al. 1988

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“…Nu' pump jluxes. The ouabain-sensitive Na+ efflux was measured in fresh human red blood cells according to a previously described method [47]. The Na+ efflux was studied as a function of various concentrations of endalin, or ouabain.…”

Section: Methodsmentioning

confidence: 99%

“…Table 2. Inhibition of the Na+ efflux catalyzed by the Na' pump in fresh human red blood cells by urine-derived Na+ ,K+ -ATPase inhibitor The Na+ efflux was measured according to a previously described method [47]. 1 unit endalin was reconstituted in 100 mM Tris/HCl, pH 7.4, and the acidic pH was adjusted to 6.0 using LiOH.…”

Section: S Imentioning

confidence: 99%

Further biochemical characterization of an Na⁺ pump inhibitor purified from human urine

Crabos

Grichois

Guicheney

et al. 1987

European Journal of Biochemistry

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An increase in endogenous Na+,K+‐ATPase inhibitor(s) with digitalis‐like properties has been reported in chronic renal insufficiency, in Na+‐dependent experimental hypertension and in some essential hypertensive patients. The present study specifies some properties and some biochemical characteristics of a semipurified compound from human urine having digitalis‐like properties. The urine‐derived inhibitor (endalin) inhibits Na+,K+‐ATPase activity and [3H]‐ouabain binding, and cross‐reacts with antidigoxin antibodies. The inhibitory effect on ATPases of endalin is higher on Na+,K+‐ATPase than on Mg2+‐ATPase and Ca2+‐ATPase. The mechanism of endalin action on highly purified Na+,K+‐ATPase was compared to that of ouabain and was similar in that (a) it reversibly inhibited Na+,K+‐ATPase activity; (b) it inhibited Na+,K+‐ATPase non‐competitively with ATP; (c) its inhibitory effect was facilitated by Na+; (d) K+ decreased its inhibitory effect on Na+,K+‐ATPase; (e) it competitively inhibited ouabain binding to the enzyme; (f) its binding was maximal in the presence of Mg2+ and Pi; (g) it decreased the Na+ pump activity in human erythrocytes; (h) it reduced serotonin uptake by human platelets; and (j) it was diuretic and natriuretic in rat bioassay. The endalin differed from ouabain in only three aspects: (a) its inhibitory effect was not really specific for Na+,K+‐ATPase; (b) its binding to the enzyme was undetectable in the presence of Mg2+ and ATP; (c) it was not kaliuretic in rat bioassay. Endalin is a reversible and partial specific inhibitor of Na+,K+‐ATPase, its Na+,K+‐ATPase inhibition closely resembles that of ouabain and it could be considered as one of the natriuretic hormones.

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“…Introduction Cicletanine (Figure 1) is a new antihypertensive furopyridine derivative which also exhibits diuretic properties. In contrast to the classical diuretics such as frusemide, amiloride and spironolactone, the renal effects of cicletanine do not seem to rely upon a direct inhibition of one of the various Na + carriers but rather upon a stimulation of the K+ fluxes (Garay et al, 1984). Since K+ efflux has been demonstrated to be associated with a stimulation of prostaglandin (PG) biosynthesis (Dusing et al, 1982) and that some PGs are vasodilator and natriuretic, namely prostacyclin (Levenson et al, 1982), it was therefore hypothetized that the diuretic effect of cicletanine could be, at least partly, a prostacyclin dependent mechanism (Dorian et al, 1984;Guinot et al, 1985;Hornych et al, 1986).…”

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confidence: 89%

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

Ferry¹,

Geoffroy²,

Pozet³

et al. 1988

Brit J Clinical Pharma

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1 The kinetics of a single oral dose (300 mg) of cicletanine a new antihypertensive drug with diuretic properties, and its effects on the urinary excretion of electrolytes and of the major stable metabolites of prostacyclin and thromboxane A2 were studied in patients with normal renal function (n = 6), mild (n = 9) and severe (n = 10) renal insufficiency. 2 In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0.4 ml min-') and its cumulative renal excretion (0.85% of the administered dose), were low. Mild renal insufficiency did not significantly alter these parameters, while severe renal impairment reduced the renal clearance and the cumulative urinary excretion of cicletanine and increased its apparent elimination half-life (31 h). However the area under the plasma curve was not changed due to reduced plasma concentrations in these patients. 3 Cicletanine induced a rapid and marked (four fold as a mean) increase in the urinary excretion of water, sodium and potassium which lasted for 6 to 10 h, in subjects with normal renal function. Renal insufficiency did not alter the slope of the calculated plasma concentration-effects curves but reduced the maximum effect observed for water, sodium and potassium. 4 A single oral dose of cicletanine did not change the urinary excretion of 6-ketoprostaglandin Fla and thromboxane B2 in the three groups of patients studied, the basal values of which being found to be closely related to the creatinine clearance. 5 It was concluded that i) from a pharmacokinetic view point, the dosage of cicletanine should only be slightly reduced in patients with a glomerular filtration rate below 30 ml min-', ii) as with most of the diuretic agents, its natriuretic properties were markedly decreased in these patients and iii) an alteration in the renal synthesis of prostacyclin or thromboxane seems unlikely to participate in the pharmacological effects of cicletanine.

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Stimulation of K+ fluxes by diuretic drugs in human red cells

Cited by 71 publications

References 12 publications

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

Further biochemical characterization of an Na⁺ pump inhibitor purified from human urine

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

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Stimulation of K+ fluxes by diuretic drugs in human red cells

Cited by 71 publications

References 12 publications

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.

Further biochemical characterization of an Na+ pump inhibitor purified from human urine

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

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Further biochemical characterization of an Na⁺ pump inhibitor purified from human urine