Effects of digoxin-specific antibody Fab fragment (Digibind) on blood pressure and renal water-sodium metabolism in 5/6 reduced renal mass hypertensive rats.
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.
Kaide
J
J
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Ura
N
N
Torii
T
T
Nakagawa
M
M
Takada
T
T
Shimamoto
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001834:Body Water / Q000378:metabolism; D002298:Cardenolides; D004077:Digoxin / Q000276:immunology*; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012503:Saponins / Q000378:metabolism*; D012964:Sodium / Q000652:urine*
D002298:Cardenolides; D007140:Immunoglobulin Fab Fragments; D012503:Saponins; C050199:digoxin antibodies Fab fragments; C034504:digoxin-like factors; D004077:Digoxin; D012964:Sodium; D009638:Norepinephrine