It has been reported that during chronic treatment with digitalis, the number of digitalis binding sites is increased in human erythrocytes [22]. From this finding a tachyphylaxis for cardiac glycosides has been postulated. We reinvestigated this problem in several groups of patients. The number of 3H-ouabain binding sites per erythrocyte in control persons (group I) was 214 +/- 60, n = 43 (means +/- SD). The dissociation constant (KD) was 1.8 +/- 0.5 nM. Thirteen patients (group II) taking cardiac glycosides only, for at least 6 months, had 281 +/- 99 (p less than 0.05) ouabain binding sites per single red cell, KD = 1.8 +/- 0.7 nM. Group III (34 patients) took digitalis for more than 6 months and diuretics for at least 3 months (352 +/- 126 (p less than 0.001), KD = 1.6 +/- 0.6). Twenty-three of these (group IV) were taking a combination with "K+-saving" diuretics (336 +/- 194 (p less than 0.01), KD = 1.6 +/- 0.5) and (group V, 11 patients) a combination with "K+-losing" diuretics (462 +/- 133 (p less than 0.001), KD = 1.4 +/- 0.4). Nine patients (group VI) had a chronic hypokalemia, mainly due to taking furosemide (437 +/- 98 (p less than 0.001), KD = 1.5 +/- 0.4). Four control persons took 50 mg hydrochlorothiazide daily for more than 4 months without measurable K+-losses and without changes in ouabain binding sites. It is concluded from these findings that diuretic treatment with chronic hypokalemia in addition to digitalis is accompanied by a significant increase in ouabain binding sites in human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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