K. Aiura et al., CIRCULATING CONCENTRATIONS AND PHYSIOLOGICAL-ROLE OF ATRIAL-NATRIURETIC-PEPTIDE DURING ENDOTOXIC-SHOCK IN THE RAT, Critical care medicine, 23(11), 1995, pp. 1898-1906
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.