Endotoxin-induced atrial natriuretic factor release: in vivo and in vitro studies.

OBJECTIVE: We evaluated the effects of coliform endotoxin on the circulating levels of atrial natriuretic factor and renal function. To understand the direct effects of endotoxin in the release of atrial natriuretic factor by cardiac tissue, studies in isolated rat atria were performed.

STUDY DESIGN: In vivo studies were used. Anesthetized dogs were studied, with one group receiving isotonic saline solution (n = 6) and the other group receiving 50 microg/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular parameters, renal function, and circulating levels of atrial natriuretic factor were measured at specified time intervals. In another set of experiments with in vitro studies left atria from Sprague-Dawley rats were isolated and perfused. In the control group (n = 9) the standard Krebs perfusate was used. In the endotoxin group (n = 9) coliform endotoxin was added at a concentration of 250 microg/mL to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriuretic factor was measured from the perfusate.

RESULTS: Administration of endotoxin resulted in decreased blood pressure (P < .05) with a concomitant increase in heart rate. Renal artery flow, however, showed an increase (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control group. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not prevent the decrease in fractional sodium excretion (P < .05) and creatinine clearance despite an increase in the urinary output. Serum sodium, serum potassium, and osmolalities, however, remained relatively stable. The study pertaining to isolated atria showed that in the presence of low atrial pressures, addition of endotoxin had no significant effect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly higher in the group directly exposed to endotoxin compared with the control group.

CONCLUSIONS: These studies demonstrate that the slow infusion of coliform endotoxin results in increased circulating levels of atrial natriuretic factor. This increase is in part due to the direct effect of endotoxin on the heart as indicated by studies in isolated atria. Our data suggest that atrial natriuretic factor in endotoxemia acts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance.