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Thiazide diuretics are particularly efficacious in the treatment of hypertension in blacks. A number of observations suggest that many hypertensive blacks have features consistent with a status of "corrected" volume expansion. Our studies, as well as those of other investigators, show that the Na,K pump is inhibited in leucocytes and erythrocytes of blacks with essential hypertension. This observation is also consistent with the concept of volume expansion in hypertensive blacks, since the Na,K pump is inhibited in many forms of experimental volume expansion, including the administration of salt in normal humans. We postulate that the efficacy of thiazide diuretics may be related to their ability to stimulate the Na,K pump. We present data obtained in 13 black hypertensive men in whom Na efflux, and Na,K-ATPase in the erythrocyte rose significantly after 7 days of treatment with hydrochlorothiazide, 50 mg/day. Diuretic therapy may indirectly result in reduced intracellular calcium in the vascular smooth muscle.

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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.