Nutrient concentrations in plasma influence neurotransmitter synthesis in the brain and periphery. Tyrosine, an essential amino acid, is the biochemical precursor for the catecholamines: epinephrine, norepinephrine, and dopamine. Since catecholamines are involved in blood pressure (BP) regulation, and mediate the sympathetic response to hemorrhage, they are of special interest to the anesthesiologist or surgeon. Tyrosine, like its catecholamine products, increases BP during hemorrhagic shock. It acts by increasing catecholamine synthesis, and not by direct receptor action or conversion to its sympathomimetic product, tyramine. Experiments are proposed to explore two possible advantages of tyrosine over traditionally-used pressors. 1) The ability of tyrosine pretreatment to blunt the BP drop following an hemorrhagic insult will be studied using an anesthetized rat model for hemorrhagic shock. Rats will be bled a defined percentage of their blood volume, and the BP response to hemorrhage observed. 2) Tyrosine's effect on renal dopamine and dopamine metabolites will be examined in rats, normotensive or hypotensive for one hour. We also propose to examien effects of diet on the BP response to hemorrhage, and the usefulness of the tyrosine/large neutral amino acid ratio predicting an animal's hemodynamic response to blood loss. The effects if hypotension on spinal cord catecholamine synthesis and release, and the possible effects of exogenous tyrosine on these neurons will be examined in rats hypotensive for one hour. Finally, the effects of hypotension per se on endogenous tyrosine dynamics, i.e., on the plasma tyrosine/large neutral amino acid ratio, brain tyrosine concentration, and on the blood-brain barrier transport system for tyrosine will be measured.
|Conlay, L A; Maher, T J; Roberts, C H et al. (1988) Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma. Neurochem Int 12:291-5|