Effects of cardiac glycosides on 24-h ambulatory blood pressure in healthy volunteers and patients with heart failure

Abstract

Blood pressure effects of cardiac glycosides in humans have been infrequently reported. Although direct infusion of ouabain or digoxin causes vasoconstriction, indirect effects of cardiac glycosides may have the opposite effect, owing to changes in sympatho-vagal balance. This paper summarises three studies on the effects of cardiac glycosides on circadian blood pressure, utilizing automatic 24-h ambulatory blood pressure measurement (ABPM). In healthy volunteers, 10 days of oral digoxin or digitoxin caused decreases in diastolic blood pressure and heart rate during overnight sleep. No effect was detectable during daytime activities. In patients with heart failure (NYHA stage II), 7 days of oral digoxin also caused a decrease in diastolic blood pressure but only a small increase in systolic pressure during overnight sleep. Again, no effect was detectable during the day. Cardiac glycosides have significant effects on blood pressure, which only appear during overnight sleep, i.e. a phase when sympathetic background activity is lowest. Regular daytime activities may 'overwrite' these effects. Effects of cardiac glycosides on blood pressure may have therapeutic impact, depending on the stage of heart failure and concomitant diseases.

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

“…Endogenous ouabain and organ damage G Nagy et al patients with heart failure treated by exogenous cardiac glycoside presuming an elevated sympathetic tone in this population. [18][19][20] In our study, the excreted level of norepinephrine assessed in morning fresh urine, positively correlates with urinary level of EO. These observations support the theory that the level of plasma EO may have a regulatory role in nighttime blood pressure profile, probably with increased sympathetic activation in hypertensive patients untreated with cardiac glycosides.…”

“…17 The orally administered cardiac glycoside (digoxin) in the therapeutic range decreased the nighttime diastolic blood pressure in healthy volunteers as well as it had in patients with heart failure a diminishing effect on the nighttime diastolic blood pressure and elevated the nighttime systolic blood pressure but it did not have an effect on daytime blood pressure profile because it is overregulated by sympathetic effects of daytime activities. [18][19][20] Production of EDLF in humans is not constant; a decreased nighttime urinary EDLF excretion has been shown in healthy volunteers. 21 Our goal was to analyse associations between plasma and urinary EO and several markers of cardiovascular status including results of echocardiography, echo-tracking and ABPM as well as other parameters as brain natriuretic peptide (BNP), nighttime catecholamines excretion, intima-media thickness (IMT) in patients with treated primary hypertension (HT), type 2 diabetes mellitus (DM) and/or chronic kidney disease (CKD).…”

Sensational site: the sodium pump ouabain-binding site and its ligands

“…But the results posed a dilemma; ouabain and digoxin both inhibit the NKA in similar fashion, yet digoxin was never reported to induce hypertension even though it was used widely to treat HF for more than two centuries. In fact, digoxin has no effect on daytime BP in healthy subjects or patients with HF, and it modestly decreases nighttime diastolic and mean BPs ( 324 ); digoxin has even been reported to lower BP in patients with hypertension ( 325 ). Therefore, one of us (JMH) tested the effect of prolonged administration of ouabain and digoxin in rats.…”