The importance of increased
endogenous digitalis-like factor (EDLF) in volume-expanded
hypertension has been generally agreed. To further clarify the role of EDLF on the development of
hypertension and renal water-
sodium handling in 5/6 reduced renal mass hypertensive rats (RRM), we studied the effects of acute administration of
digoxin-specific antibody
Fab fragment (
Digibind) in the early phase and the chronic phase of
hypertension in RRM. RRM and
sham-operated rats were given 1% saline for 1 or 4 weeks. RRM were injected
Digibind (60 mg/kg) or vehicle (
0.9% saline) intravenously in the first or fourth week under
thiobutabarbital anesthesia. All
sham-operated rats were administered
Digibind under the same condition.
Digibind altered neither blood pressure, heart rate, urine volume, nor urinary
sodium excretion in
sham-operated rats. However,
Digibind produced a gradual but significant decline in mean arterial pressure to the level slightly above that in
sham-operated rats from 153 +/- 5 to 131 +/- 5 mm Hg in the first week and from 181 +/- 6 to 129 +/- 4 mm Hg in the fourth week without any significant change in heart rate. The decrease in mean arterial pressure at 160 min after
Digibind administration in the fourth week (-48 +/- 5 mm Hg) was greater than that in the first week (-22 +/- 4 mm Hg). No differences were observed in urine volume, urinary
sodium excretion, or plasma
norepinephrine concentration between
Digibind and vehicle-treated RRM in either week. These data suggest that EDLF would contribute to both the early and chronic phase in the development of
hypertension in RRM.