Hemodynamic effects of bufalin in the anesthetized dog.

Abstract

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 /xg/min with brachial arterial blood flow held constant at 100 ml/min produced a dosedependent 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

Role of dietary salt in hypertension

“…Bufalin, a member of the same class and closely related to another inhibitor (resibufagenin), is of interest because it has all the physiological actions expected of a Na + ,K + -ATPase inhibitor; it blocks potassium vasodilation, potentiates norepinephrine vasoconstriction, increases vascular resistance, increases left ventricular dp/dt, raises arterial pressure, and produces natriuresis and diuresis (Oda et al, 2001;Eliades et al, 1989Eliades et al, , 1991Pamnani et al, 1991;Cress et al, 1991). In the rat and dog, the pressor effect is seen on chronic administration (Pamnani et al, 1994) as well as acutely (Eliades et al, 1989).…”

“…In the rat and dog, the pressor effect is seen on chronic administration (Pamnani et al, 1994) as well as acutely (Eliades et al, 1989).…”

Effects of bufalin on norepinephrine turnover in canine saphenous vein.

“…It also significantly inhibits [ Here there is another property bufalin shares with the cardiac glycosides, one that could contribute to its ability to activate cardiac and vascular smooth muscle 9 by increasing the concentration of norepinephrine in the neurovascular junction.…”

“…6 In this research we used the steroid bufodienolide bufalin ( Figure 1) as a model of an endogenous DLF since resibufogenin is not commercially available. Bufalin is a potent inhibitor of Na + ,K + -ATPase 7 ' 8 and a stimulator of cardiovascu-lar muscle contractile activity, 9 is readily available commercially, and is almost identical in structure (differing only by one H + ) (Figure 1) to the only chemically identified mammalian endogenous DLF, resibufogenin, a bufodienolide found in amphibians. 10 If the bufodienolides are to be considered candidates for the endogenous DLF, they should block K + -mediated vasodilation, potentiate norepinephrine vasoconstriction, increase vascular resistance, increase left ventricular dP/dt, raise arterial blood pressure, and produce natriuresis and diuresis, since all of these changes result from inhibition of Na + -K + pump activity with the cardiac glycosides.…”

My forty-three years with in situ small and large blood vessels.

“…It is now clear that the cardiac glycosides (e.g., ouabain and strophanthidin) and ouabain-like steroids of animal origin such as bufalin can constrict blood vessels, raise blood pressure, increase cardiac contractility, and cause natriuresis and diuresis. 42 - 43 Resibufogenin, structurally almost identical to bufalin, has been identified as a ouabain-like agent in toad skin and plasma.…”