Inhibition of Acetylcholinesterase Modulates the Autoregulation of Cerebral Blood Flow and Attenuates Ischemic Brain Metabolism in Hypertensive Rats

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Abstract
We designed the present study to examine whether or not the inhibition of acetylcholinesterase modulates cerebral microcirculation in hypotension and improves brain metabolism in ischemia induced by bilateral carotid artery occlusion in hypertensive rats. Blood flow to the parietal cortex was determined by the H2 clearance method. Lactate, pyruvate, and ATP were estimated by enzymatic methods. Acetylcholinesterase inhibitor (AChEI, ENA-713), at 0.05, 0.1, or 0.5 mg/kg, was intravenously injected 10 min before either hemorrhagic hypotension or cerebral ischemia. The levels of acetylcholine in the control were 29.3 ± 8.1 (mean ± SD) and 39.5 ± 8.1 pmol/mg in the cortex and hippocampus, respectively, and they were significantly decreased by 15–19% after 60 min of ischemia in the vehicle-treated rats. AChEI preserved the levels to 93–98% of the control (p < 0.05 versus vehicle). The lower limit of autoregulation was 74 ± 9% of the resting values. The administration of AChEI helped preserve blood flow and lowered the limit to 64 ± 6% (p < 0.05 versus control). After 60 min of ischemia, lactate increased 6.5-fold and ATP decreased to 64% of the control value. The administration of AChEI dose-dependently reduced the lactate level 1.9- to 3.9-fold and well preserved the ATP level to 94–97% of the control. The inhibition of acetylcholinesterase activity may preserve cerebral autoregulation during hypotension and protect cerebral metabolism against ischemic insult.