Hormonal, metabolic and hemodynamic responses to central and peripheral cholinergic amplification in humans

We used the cholinesterase inhibitors physostigmine, which enters the CNS, and edrophonium, which does not, to probe the endocrine and metabolic effects of central and peripheral endogenous sympathochromaffin activation in normal humans. Eight normal young adults received an intravenous injection of edrophonium, with blood sampling for 30 min, followed after 2 h by a 10 min intravenous infusion of physostigmine salicylate with blood sampling for 100 min. Peripheral cholinergic amplification with edrophonium produced sympathetic neural stimulation (increments in plasma norepinephrine from 0.73±0.11 to 1.00±0.13 nmol/l, P=0.0045, with small, biologically inactive increments in epinephrine) resulting in rapid increments in plasma glucose (P=0.0359), serum nonesterified fatty acid (P=0.0161) and blood alanine (P=0.0209) concentrations. Apparent increments in blood β-hydroxybutyrate (P=0.0898) and lactate (P=0.0672) levels were not statistically significant. There were no significant changes in heart rate or blood pressure. Central cholinergic amplification with physostigmine produced predominantly adrenomedullary stimulation (increments in plasma epinephrine from 80±10 to 620±320 pmol/l, P=0.04, without increments in norepinephrine), with increments in plasma glucose (P=0.04) concentrations and an apparent, but not significant, increase in serum non-esterified fatty acid levels (P=0.09). Plasma cortisol levels increased (P=0.0037); an apparent increase in plasma growth hormone levels was not statistically significant (P=0.21). There were prominent increments in heart rate (P=0.01), systolic blood pressure (P=0.0032) and diastolic blood pressure (P=0.04). The latter suggests a component of sympathetic neural stimulation. Neither drug altered the plasma concentrations of insulin, C-peptide, or glucagon significantly. Apparent increments in pancreatic polypeptide levels were not significant (P=0.12 and 0.16 respectively). Thus, these cholinesterase inhibitors can be used to dissect functionally endocrine and metabolic responses to sympathetic neural and adrenomedullary activation respectively in humans.