Endogenous atrial natriuretic factor is involved in the natriuresis following sodium loading in rats with chronic heart failure

• Published in: Cardiovascular research Vol. 25; no. 7; pp. 558 - 564
• Main Authors: Drexler, Helmut, Hirth-Dietrich, Claudia, Stasch, Johannes-Peter, Neuser, Dieter, Gross, Rainer, Kauczor, Hans-Ulrich, Just, Hanjörg, Kazda, Stanislav
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.1991
• Subjects: Animals; atrial natriuretic factor; Atrial Natriuretic Factor - antagonists & inhibitors; Atrial Natriuretic Factor - blood; Biological and medical sciences; Cardiology. Vascular system; cyclic GMP; Cyclic GMP - urine; Heart; Heart Failure - physiopathology; Heart Failure - urine; Male; Medical sciences; monoclonal antibody; Myocardial Infarction - physiopathology; Myocardial Infarction - urine; natriuresis; Natriuresis - physiology; Potassium - urine; Rats; Sodium - urine; Heart; Animal model; Cardiac performance; Pathophysiology; Cardiovascular disease; Atrial natriuretic peptide; Isolated organ; Natriuretic hormone; Immunological investigation; Animal; Heart disease; Evolution; Left ventricle performance
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/25.7.558

Study 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. Design — A monoclonal antibody against atrial natriuretic factor was used for specific antagonisa-tion 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. Experimental material — 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. Measurements and main 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) ν 5.8(1.2) nmol·kg−1, p<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) μmol·kg−1 (p<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.