Plasma catecholamines during endotoxin infusion in conscious unrestrained rats: effects of adrenal demedullation and/or guanethidine treatment.

We have examined the effect of E coli endotoxin infusion (41 micrograms kg-1 min-1 iv for 4 h) on plasma concentrations of epinephrine (E), norepinephrine (NE), and dopamine (DA) in the conscious unrestrained rat. Saline infusion did not change catecholamine concentrations from the preinfusion values of 230.8 +/- 32.9 pg ml-1 (E), 456.8 +/- 104.9 pg ml-1 (NE), and 49.0 +/- 19.9 pg ml-1 (DA). Endotoxin produced marked elevations in all three catecholamines. At 1 h, the plasma concentrations were 3,279 +/- 494.6 pg ml-1 (E), 1,670 +/- 137.0 pg ml-1 (NE), and 191.5 +/- 13.7 pg ml-1 (DA). Thereafter, concentrations of E decreased whereas concentrations of NE and DA increased. These increases were prevented by a combination of adrenal demedullation (28 days previously) and treatment with guanethidine (25 mg kg-1 iv, -24 h) ("sympathectomy"). Guanethidine alone markedly reduced the peak NE concentrations without affecting the E concentrations or the 1-h NE concentrations. Demedullation alone prevented the increase in E and reduced the 1-h NE concentrations. Survival in such "sympathectomized" animals was markedly reduced (survival at 4 h in rats receiving endotoxin alone, 100%: in "sympathectomized" animals receiving endotoxin, 12.5%). The tachycardia produced by endotoxin was attenuated in "sympathectomized" rats and mean arterial blood pressure fell rapidly. Endotoxin-induced hyperglycemia was prevented by "sympathectomy" and hypoglycemia was evident as early as 1 h after commencing the infusion. Endotoxin produced hypoinsulinemia in normal rats but did not change plasma insulin values in "sympathectomized" animals, although these animals showed a pre-endotoxin fasting hyperinsulinemia. An important protective role for catecholamines is suggested, especially in the early stages of shock.