Norepinephrine

Description
Norepinephrine is a neurotransmitter in the catecholamine family. It mediates chemical communication in the sympathetic nervous system. Like other neurotransmitters, it is released at synaptic nerve endings to transmit the signal from a nerve cell to other cells. Norepinephrine is almost identical in structure to epinephrine, which is released into the bloodstream from the adrenal medulla under sympathetic activation. Both of these are indicators of a stress respopnse. (http://www.encyclopedia.com/html/n1/norepine.asp).

Significance
High plasma norepinephrine levels have been associated with increased mortality (Reuben et al., 2000), however, normal aging is associated with an increase in plasma norepinephrine levels as well (Wallin et al., 1981; Ziegler et al, 1976; Christensen, 1982). With advancing age there is decreased clearance of norepinephrine (Esler et al., 1995).

Plasma norepinephrine is primarily derived from the small portion of neurotransmitter that escapes reuptake and metabolism at adrenergic synapses throughout the body (Young & Landsberg, 1998). High plasma norepinephrine levels have been associated with reduced survival in healthy older persons (Christensen, & Schultz-Larsen, 1994) as well as in patients with congestive heart failure (Semeraro et al., 1997), and previous myocardial infarction (Boldt et al., 1995).

Method of measurement
Norepinephrine is excreted with the urine. Because levels vary over the day, 12 hour or 24 hour urine collections are used. Can be normalized by creatinine excretion to adjust for body size (Karlamangla et al., 2005). To adjust for body size, results for norepinephrine are reported as micrograms norepinephrine per gram creatinine of urine excretion (Reuben et al., 2000). Determinations can be made with high-pressure liquid chromatography (Krsulovic, 1983).

There are no normative values for urinary norepinephrine and epinephrine levels. High catecholamine levels can be classified as levels falling within the top tertile or the top quartile of norepinephrine for a sample. In the MacArthur Study the cut off was 48.00 ug/g creatinine.

A blood plasma test is also available, although used more rarely.

References
· Boldt, J., Menges, T., Kuhn, D., Diridis, C., & Hempelmann, G.L. (1995). Alterations in circulating vasoactive substances in the critically ill: A comparison between survivors and non-survivors. Intensive Care Medicine, 21, 218-225.
· Christensen, N.J. (1982). Sympathetic nervous activity and age. European Journal of Clinical Investigation, 12, 91-92.
· Christensen, N.J., & Schultz-Larsen, K. (1994). Resting venous plasma adrenalin in 70-year men correlated positively to survival in a population study. Journal of Internal Medicine, 235, 229-232.
· Encychopeida.com. (2005). Norepinephrine. Retrieved from March 28, 2005, from http://www.encyclopedia.com/html/n1/norepine.asp
· Esler, M.D., Turner, A.G., Kaye, D.M., Thompson, J.M., Kingwell, B.A., Morris, M., et al. (1995). Aging effects on human sympathetic neuronal function. American Journal of Physiology, 268, R278-R285.
· Karlamangla, A.S., Singer, B.H., Greendale, G.A., & Seeman, T.E. (2005). Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging. Psychoneuroendocrinology, 30(5), 453-460.
· Krsulovic, A.M. (1983). Investigations of catecholamine metabolism using high performance liquid chromatography: Analytical methodology and clinical applicators. Journal of Chromatography, 9, 1-34.
· Reuben, D.B., Talvi, S.L., Rowe, J.W., & Seeman, T.E. (2000). High urinary catecholamine excretion predicts mortality and functional decline in high-functioning, community-dwelling older persons: MacArthur Studies of Successful Aging. Journal of Gerontology: Medical Sciences, 55(10), M618-M624.
· Semeraro, C., Marchini, F., Ferlenga, P., Masotto, C., Morazzoni, G., Pradella, L., et al. (1997). The role of dopaminergic agonists in congestive heart failure. Clinical and Experimental Hypertension,19(1&2), 201-215.
· Wallin, B.G., Sundlof, G., Eriksson, B., Dominiak, P., Grobecker, H., & Lindblad, L.E. (1981). Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiologica Scandinavica, 111, 69-73.
· Young, J.B., & Landsberg, L. (1998). Catecholamines and the adrenal medulla. In J.D. Wilson, D.W. Foster, H.M. Kroenberg, & P.R. Larsen (Eds.), Williams Textbook of Endocrinology, (9th Edition, pp.665-728). Philadelphia, PA: W.B. Saunders.
· Ziegler, M.G., Lake, C.R., & Kopin, I.J. (1976). Plasma noradrenaline increases with age. Nature, 261, 333-334.