H. Krep et al., VOLUME-SENSITIVE HYPERTENSION AND THE DIGOXIN-LIKE FACTOR - REVERSAL BY A FAB DIRECTED AGAINST DIGOXIN IN DOCA-SALT HYPERTENSIVE RATS, American journal of hypertension, 8(9), 1995, pp. 921-927
Although volume and vasoconstriction have been considered polar elemen
ts in a useful pathogenetic hypertension model, many observations sugg
est that vasoconstriction is involved in volume-dependent hypertension
, reflecting the effect of a digitalis-like factor. To examine that po
ssibility, we assessed the depressor responses to Digibind, an antibod
y Fab directed against digoxin, in a volume-dependent model-DOCA-salt-
induced hypertension in rats. Digibind (10 mg/kg, intravenously) induc
ed a gradual blood pressure fall over 2 h that was sustained for 4 h (
P < .001). Blood pressure did not fall with Digibind when DOCA was adm
inistered without salt or a high-salt intake was provided without DOCA
. The intracellular sodium content of the rat aorta, measured by atomi
c absorption spectroscopy after cold choline wash, was increased in th
e DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (1
2.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with b
lood pressure, was not increased either by dietary salt supplementatio
n without DOCA, or by DOCA with a low-salt diet. Sodium pump activity
was measured as Rb-86 uptake into vascular smooth muscle (VSM). Both o
uabain-sensitive and ouabain-resistant Rb-86 uptake were significantly
higher in VSM from DOCA-high-salt animals (P < .01). Despite its effe
ctiveness in reducing blood pressure in this model, Digibind influence
d neither VSM sodium content nor Rb-86 uptake, The results are consist
ent with a role for a circulating digitalis-like factor in this volume
-dependent model, but events at the VSM level are complex.