The present study examines in detail the short-term cardiovascular actions of
atrial natriuretic factor (
ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of
congestive heart failure (CHF) were apparent after the 14 days, characterized by
low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of
ANF,
noradrenaline,
arginine vasopressin and
renin, and marked fluid retention. On day 14 of pacing,
intravenous infusion of
ANF at 100 micrograms/h for 60 min restored cardiac output to prepacing values and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma
renin, or
noradrenaline levels. These hemodynamic changes, produced by short-term infusion of
ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that
ANF improves cardiac function in conscious sheep with CHF, primarily by a
vasodilator action to reduce cardiac preload, and suggests that
ANF may be useful in treating the hemodynamic effects associated with
cardiac failure.