Circulation, Vol 77, 398-406, Copyright © 1988 by American Heart Association
GA Riegger, D Elsner, EP Kromer, C Daffner, WG Forssmann, F Muders, EW Pascher and K Kochsiek
In an animal preparation of congestive heart failure in the dog, during the
development of cardiac failure due to rapid right ventricular pacing we
observed significant decreases in cardiac output and arterial pressure and
increases in pulmonary arterial and right atrial pressure. We also observed
a related increase in right atrial pressure and increases in plasma levels
of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate
(c-GMP). Ultrastructure changes in the atrial myoendocrine cells indicated
extreme stimulation of the secretory apparatus of ANP. The response of
hemodynamic, renal, and hormonal variables was investigated after
incremental infusions (0.01, 0.03, 0.1, 0.3, and 0.06 microgram/kg/min) of
exogenous ANP. In healthy animals ANP significantly decreased mean arterial
pressure, cardiac output, stroke volume, and right atrial pressure without
changing heart rate or peripheral vascular resistance. As expected, we
found a striking increase in urine flow and urinary excretion of sodium,
chloride, magnesium and calcium and a smaller increase in potassium
excretion. ANP suppressed renin secretion, and increased renal plasma flow,
glomerular filtration rate, and filtration fraction. In dogs with heart
failure ANP caused a small reduction in mean arterial pressure. No effect
was seen on other hemodynamic variables or plasma renin concentration. The
excretory effects on the kidneys were completely absent, and smaller
increases in glomerular filtration rate and filtration fraction were
observed. We found no difference between healthy dogs and animals with
heart failure with respect to the secretion of c-GMP during ANP infusions
in relation to the plasma levels of ANP. This suggests an intracellular
defect that prevents the mediation of the hormonal signal into biological
action in the presence of heart failure.
ARTICLES
Atrial natriuretic peptide in congestive heart failure in the dog: plasma levels, cyclic guanosine monophosphate, ultrastructure of atrial myoendocrine cells, and hemodynamic, hormonal, and renal effects
Medizinische Universitatsklinik Wurzburg, F.R.G.
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