Plasma digitalislike activity in essential hypertension or end-stage renal disease.

Abstract

SUMMARY Plasma extracts from 119 subjects showed a digitalislike activity, as evidenced by the ability of these extracts to inhibit ouabain binding to the Na + -K + pump. High levels of the digitalislike compound were found in 18 of 54 untreated hypertensive subjects, 7 of 21 normotensive subjects with a family history of hypertension, and 10 of 14 patients with end-stage renal failure. Dialysis significantly reduced the activity of this compound. These results suggest 1) that endogenous digitalislike factor is not directly linked to hypertension but rather is related to sodium balance and 2) that it neither originates nor is activated by renal tissue, as it was present in four of six anephric patients. (Hypertension 8: 632-638, 1986) KEY WORDS • Na + -K + -ATPase • ouabain • essential hypertension • chronic renal failure • dialysis • hypertensive heredity T HE renal regulation of sodium and water homeostasis is mediated by intrarenal, physical, and hormonal factors and by extrarenal hormones. The latter include factors retaining Na + and water, such as aldosterone and antidiuretic hormone, and factors eliminating Na + in the urine while the Na + balance is positive. The existence of a humoral natriuretic factor inhibiting renal tubular Na + reabsorption was inferred from various experiments in the 1960s showing that the natriuresis following acute and chronic Na + loading could not be explained by changes in aldosterone, vasopressin, or the glomerular filtration rate.

The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation

“…Although several studies have shown a correlation between elevated endogenous cardiac glycosides and certain pathological conditions, the physiological function of endogenous cardiac glycoside-like compounds is still uncertain (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17).…”

“…Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17). In addition, marked increases in endogenous ouabain-like compounds occur in congestive heart failure, both in animal models and human patients (18)(19)(20).…”

Heparin, Fatty Acids and Sodium, Potassium-ATPase Inhibition by Plasma Factors during Hemodialysis

“…Comparison is difficult because red cells were used as the target for plasma inhibitors and because of lack of information about heparin, and the time specimens were taken in relation to dialysis [27,29].…”

The sodium pump and hypertension: A physiological role for the cardiac glycoside binding site of the Na,K-ATPase

“…The identification of cardiac glycoside-like molecules in mammals has led to the proposal that these compounds are natural regulators of Na,K-ATPase in vivo (7)(8)(9)(10). Several studies have shown a correlation between these cardiac glycoside-like molecules and certain pathological conditions, such as hypertension and heart failure (11)(12)(13)(14)(15)(16)(17). Plasma levels of these putative ligands for the Na,KATPase are high in several animal hypertension models, as well as in human essential hypertension and preeclampsia (11-14, 18, 19).…”