Hemodynamic effects of bufalin in the anesthetized dog

Studies in Lichstein's laboratory suggest that the endogenous digitalislike substance implicated in low renin hypertension might be a steroidal dienolide derivative. If this is true, the bufadienolides should block potassium vasodilation and enhance norepinephrine vasoconstriction, constrict blood vessels, raise blood pressure, and produce natriuresis and diuresis. We have therefore examined these parameters while infusing bufalin (aglycone), a bufadienolide, intrabrachially and intravenously in the anesthetized dog. Intrabrachial infusion of 5-25 micrograms/min with brachial arterial blood flow held constant at 100 ml/min produced a dose-dependent increase in perfusion pressure with rapid onset and offset, a progressive decrease in the vasodilator response to intrabrachial injection of 1 ml iso-osmotic potassium chloride solution (but not to acetylcholine), and an increase in the vasoconstrictor response to intrabrachial injection of 0.1 microgram norepinephrine. Intravenous infusion at 5-50 micrograms/min produced a dose-dependent increase in systemic arterial blood pressure, rate of change of ventricular pressure (dP/dt), and after the highest dose, cardiac irregularities. Natriuresis and diuresis were not observed. Thus, bufalin does in fact have some of the physiological properties required to be considered a candidate for the digitalislike substance found in low renin hypertension.