Endogenous atrial natriuretic factor is involved in the natriuresis following sodium loading in rats with chronic heart failure.
OBJECTIVE
Plasma levels of atrial natriuretic factor are increased in chronic heart failure; however, it is still controversial whether these raised levels contribute to the diuresis and natriuresis in this setting. To address this issue the potential contribution of endogenous atrial natriuretic factor in the renal excretion of a moderate oral sodium load in a rat model of chronic heart failure was studied.


METHODS
A monoclonal antibody against atrial natriuretic factor was used for specific antagonisation of its in vivo effects. Animals were subjected to oral sodium loading (30 ml.kg-1 0.9% NaCl, 2.5% dextrose) at baseline, immediately after, and 5 d after injection of monoclonal antibody or control solvent.


METHODS
Sham operated rats and rats with chronic heart failure due to myocardial infarction (infarct size 35(SEM 4)% of left ventricle) were studied 4-5 weeks after surgery.


RESULTS
The renal excretion of cyclic guanosine monophosphate (cGMP), which represents a specific marker for the activation of the atrial natriuretic factor system, was markedly increased in infarcted rats, at 17.9(SEM 3.4) vs 5.8(1.2) nmol.kg-1, p less than 0.01. Atrial natriuretic factor antibody given immediately before sodium loading reduced the natriuretic response (0-4 h period) in infarcted rats from 1270(171) to 805(76) mumol.kg-1 (p less than 0.01) but not in sham operated animals. Similarly, the excretion of cGMP was only decreased by atrial natriuretic factor antibody in infarcted rats, from 29.8(6.3) to 20.7(3.7) nmol.kg-1. The reduction in sodium and cGMP excretion in infarcted rats was confirmed with a purified antibody preparation.


CONCLUSIONS
Endogenous atrial natriuretic factor appears to be involved in the natriuresis following a moderate oral volume load in chronic heart failure. Thus the raised concentrations found in chronic heart failure may contribute to the regulation of urinary sodium excretion under these conditions despite the fact that the diuretic effects of exogenous atrial natriuretic factor are attenuated in chronic heart failure.
Drexler
H
H
Medizinische Klinik III, Universität Freiburg, Germany.
Hirth-Dietrich
C
C
Stasch
J P
JP
Neuser
D
D
Gross
R
R
Kauczor
H U
HU
Just
H
H
Kazda
S
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000097:blood*; D006152:Cyclic GMP / Q000652:urine; D006333:Heart Failure / Q000503:physiopathology / Q000652:urine*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000652:urine; D009318:Natriuresis / Q000502:physiology*; D011188:Potassium / Q000652:urine; D051381:Rats; D012964:Sodium / Q000652:urine
D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D011188:Potassium