Effects of Digoxin on the Vascular Reactivity to Infused Norepinephrine in Normotensive Subjects

In order to clarify the role of a circulating digitalis-like substance in the pathogenesis of essential hypertension, short (intravenous) and long term (oral administration) effects of digoxin on the vascular reactivity to infused norepinephrine (NE) at a constant rate (0.22 μg/kg/min) were studied in normotensive male volunteers.
In 14 subjects 90 min after intravenous administration of digoxin, basal intraerythrocytic sodium concentration (ENa) before NE infusion was significantly increased due to inhibition of Na+, K+ ATPase activity in cell membrane by digoxin indicated as erythrocyte ouabain sensitive efflux rate constant (ERCos), and basal plasma NE concentration (PNE) was significantly increased. Basal hemodynamic parameters except for heart rate (HR) remained unchanged, but increases in mean blood pressure and total peripheral resistance during NE infusion (△MBP and △TPR) were significantly augmented. Increase in PNE during NE infusion (△PNE) tended to decrease. Intravenous administration of digoxin significantly augmented △MBP/ △PNE and △TPR/ △PNE as the parameters for the pressor response and vascular reactivity to NE from 3.81 ± 1.64 mmHg•ml•ng^-1 to 4.85 ± 2.12 mmHg•ml•ng^-1 and from 121 ± 75 dyne•sec•cm^-2•ng^-1 to 147 ± 61 dyne•sec•cm^-2•ng^-1, respectively.
In 14 subjects after 6 days oral administration of digoxin as well as intravenous administration of digoxin, basal ERCos was significantly inhibited and basal ENa was significantly increased. Basal PNE was unchanged, but △PNE was significantly decreased. Oral administration of digoxin also significantly augmented the pressor response and vascular reactivity to NE from 5.14 ± 1.70 mmHg•ml•ng^-1 to 6,25 ± 2.00 mmHg•ml•ng^-1 and from 130 ± 65 dyne•sec•cm^-2•ng^-1 to 176 ± 53 dyne•sec•cm^-2•ng^-1, respectively.
These findings suggest that the augmented pressor response to NE is caused by the enhanced vascular reactivity to NE through inhibition of Na+, K+ ATPase activity in cell membrane by digoxin. Thus, a circulating digitalis-like substance may play an important role in the pathogenesis of essential hypertension.