Haemodynamic effects of intact digoxin antibody and its Fab fragments in experimental hypertension.
The effects of i.v. injection of intact digoxin antibody (0.3 mg/rat) and of its Fab fragment (40 mg/rat) on blood pressure, cardiac output and total peripheral resistance were measured in conscious spontaneously hypertensive and deoxycorticosterone hypertensive rats. In vitro findings showed that Fab fragment bound radio-labelled digoxin, digitoxin and ouabain more efficiently than did intact antibody. In vivo, Fab fragment prevented the increase of total peripheral resistance induced by i.v. injection digoxin. However, Fab fragment of digoxin antibody did not alter blood pressure, cardiac output or total peripheral resistance in normal and salt-loaded spontaneously hypertensive rats (SHR) in uraemic SHR and in deoxycorticosterone hypertensive rats. We confirmed that intact digoxin antibody--bearing Fc domains with complement activating properties--lowered blood pressure in SHR and in deoxycorticosterone hypertension. This was due to a decrease in total peripheral resistance. Our data suggest that a circulating endogenous digitalis-like factor is unlikely to be important in blood pressure regulation in salt-loaded hypertension in the rat.
Department of Medicine, German Hypertension Research Institute, University of Heidelberg.
J F
JF
Mann
R
R
Miemietz
U
U
Ganten
E
E
Ritz
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D003900:Desoxycorticosterone; D004077:Digoxin / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000008:administration & dosage; D014655:Vascular Resistance
D007140:Immunoglobulin Fab Fragments; D012982:Sodium, Dietary; D003900:Desoxycorticosterone; D004077:Digoxin