CIRCULATING CONCENTRATIONS AND PHYSIOLOGICAL-ROLE OF ATRIAL-NATRIURETIC-PEPTIDE DURING ENDOTOXIC-SHOCK IN THE RAT

Objectives: To determine if there are changes in circulating concentra tions of endogenous atrial natriuretic peptide and the physiologic rol e of this peptide in endotoxic shock. Design: A prospective, randomize d, controlled animal trial. Setting: University research laboratory. S ubjects: Anesthetized male Wistar rats, weighing 250 to 350 g. Interve ntions: Six rats received 1.5 mg/kg body weight of lipopolysaccharide alone. Five rats received 1.5 mg/kg of lipopolysaccharide and 200 mu L /100 g body weight of rabbit anti-atrial natriuretic peptide serum. An other five rats received 1.5 mg/kg of lipopolysaccharide and normal ra bbit serum in the same volume as the antiserum. Measurements and Main Results: Plasma concentrations of atrial natriuretic peptide, arginine vasopressin, and aldosterone were measured, and changes in hemodynami c parameters and renal function were monitored in rats with endotoxic shock. after catheterization of the right jugular vein. Urine volume, urine sodium excretion, urinary potassium excretion, and urine 3', 5'- cyclic guanosine monophosphate (cGMP) excretion were measured at 12-hr intervals. The plasma atrial natriuretic peptide concentration was sl ightly but significantly lower 30 mins after the lipopolysaccharide in jection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01) and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL,p < .01 vs. 0 time) and remaining at higher concentrations than before the preinjection value, up to 24 hrs. In contrast, acute spike- like increases of arginine vasopressin and aldosterone concentrations were observed 30 mins after the lipopolysaccharide injection, precedin g the increase of the plasma atrial natriuretic peptide concentration. Measurements of urine volume and urine sodium excretion showed oligur ia during the initial 12 hrs after the lipopolysaccharide injection, f ollowed by diuresis and natriuresis during the subsequent 12 hrs. In a ddition, injection with anti-atrial natriuretic peptide serum in the d iuretic phase 12 hrs after the lipopolysaccharide injection significan tly inhibited the diuresis, natriuresis, and urine cGMP excretion in t his model. Furthermore, the plasma aldosterone concentration 24 hrs af ter the lipopolysaccharide injection was significantly increased by th e administration of the antisera. Conclusions: These findings suggest that endogenous atrial natriuretic peptide increases in the acute phas e of endotoxic shock and plays an important role in water and electrol yte balance by regulating diuresis.