The aim of this proposal is to determine the effect of microgravity on the autonomic nervous system, combining physiologic, biochemical, and pharmacological approaches. The hypothesis of this proposal is that altered autonomic nervous system function occurs in weightlessness and is responsible for many of the physiologic response to microgravity. The proposal has specific aims as follows: 1) To determine if human subjects adapt to microgravity with a reduction in sympathetic activity. 2) To determine the role of afferent/central mechanisms in the adaptation of the autonomic nervous system to microgravity. 3) To determine if the decrease in plasma norepinephrine produced by microgravity is due to inhibition of norepinephrine release or enhanced norepinephrine clearance. 4) To determine the effect of microgravity on postsynaptic adrenoreceptor sensitivity. 5) To determine the autonomic neuropharmacology of promethazine, which is often used as anti-nausea in space flight. In the ground-based, preflight, and the Neurolab mission, plasma and urinary catecholamines and their metabolites will be assayed using HPLC with electrochemical detection, to define circulating levels of norepinephrine, epinephrine and dopamine, their response to exercise, and their intra- and extra-neural metabolism. Tracer doses of tritiated norepinephrine will be administered to assess norepinephrine spillover and determine whether alterations in clearance or release are responsible for the decreased plasma levels seen during space flight. Sympathetic nerve traffic will be directly measured with microneurography and compare the response of efferent sympathetic activity to physiologic stimuli such as carotid baroreflex, loading and unloading with a neck chamber and skeletal muscle afferent stimulation with isometric and isotonic forearm exercise. Sympathetic baroreflex function will be tested with pharmacologic stimuli (phenylephrine and nitroprusside). The number of affinity of beta-adrenergic receptors on lymphocytes and alpha 2- adrenergic receptors on platelet will be also measured before and during exposure to microgravity. Isoproterenol and phenylephrine will be used to quantitated the sensitivity of alpha 1 and beta-adrenergic receptors function. Finally, the effect of promethazine will be defined.
Showing the most recent 10 out of 39 publications
