ENDOTOXIN-INDUCED ATRIAL-NATRIURETIC-FACTOR RELEASE - IN-VIVO AND IN-VITRO STUDIES

OBJECTIVE: We evaluated the effects of coliform endotoxin on the circu lating levels of atrial natriuretic factor and renal function. To unde rstand the direct effects of endotoxin in the release of atrial natriu retic factor by cardiac tissue, studies in isolated rat atria were per formed. STUDY DESIGN: In vivo studies were used. Anesthetized dogs wer e studied, with one group receiving isotonic saline solution (n = 6) a nd the other group receiving 50 mu g/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular paramete rs, renal function, and circulating levels of atrial natriuretic facto r were measured at specified time intervals. In another set of experim ents with in vitro studies left atria from Sprague-Dawley rats were is olated and perfused. In the control group (n = 9) the standard Krebs p erfusate was used. In the endotoxin group (n = 9) coliform endotoxin w as added at a concentration of 250 mu g/ml to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriureti c factor was measured from the perfusate. RESULTS: Administration of e ndotoxin resulted in decreased blood pressure (P < .05) with a concomi tant increase in heart rate. Renal artery flow, however, showed an inc rease (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control gro up. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not p revent the decrease in fractional sodium excretion (P < .05) and creat inine clearance despite an increase in the urinary output. Serum sodiu m, serum potassium, and osmolalities, however, remained relatively sta ble. The study pertaining to isolated atria showed that in the presenc e of low atrial pressures, addition of endotoxin had no significant ef fect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly h igher in the group directly exposed to endotoxin compared with the con trol group. CONCLUSIONS: These studies demonstrate that the slow infus ion of coliform endotoxin results in increased circulating levels of a trial natriuretic factor. This increase is in part due to the direct e ffect of endotoxin on the heart as indicated by studies in isolated at ria. Our data suggest that atrial natriuretic factor in endotoxemia ac ts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance.