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To investigate the interaction of cardiac glycosides with vasoconstrictors, we examined the effects of short term treatment with the cardiac glycoside digoxin (6 mg/kg/day, i.p., for 6 days) in rats made hypertensive by chronic infusion of norepinephrine (NE), angiotensin II (A II) or vasopressin (VP). When digoxin was administered simultaneously with NE at 1.8 mg/kg/day (i.p.) by use of osmotic minipumps in conscious rats, systolic blood pressure decreased to 120 +/- 3 mmHg on Day 1 whereas it rose to 148 +/- 2 mmHg in rats given NE alone (p less than 0.01). The antihypertensive effect of digoxin was sustained for the entire experimental period and was not associated with any change in urinary sodium excretion. When the same dose of digoxin was administered simultaneously with A II at 900 micrograms/kg/day (i.p.) in conscious rats, systolic blood pressure rose to a greater extent than in those given A II alone. The administration of digoxin had no effect on the blood pressure elevation induced by chronic infusion of VP at a rate of 7.2 U/kg/day (i.p.). It is concluded that short term treatment with digoxin has a variety of effects on blood pressure in rats; pressor, depressor, or is no effects depending upon vasoconstrictor used.

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.