Norepinephrine Effects On the System

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1 Norepinephrine Effects On the System NE Conversion to Epinephrine in the Circulation Under stress, the increased norepinephrine produced is transmitted throughout the system. This increased level represents an increased charge to the whole system. There is a slow leak of norepinephrine from every sympathetic nerve fiber. There is sympathetic innervation to every blood vessel in the system. The sympathetic neurons are wrapped around all the arteries and arterioles and cause vasospasm (cold hands and feet) with anxiety. With aging or prolonged stress, the norepinephrine level will continuously increase. Much of this ever-increasing NE level is in response to the increased difficulties of aging adults from many physical, financial and social stressors. However, from a physiologic standpoint, the ravages of old age come from stressdriven inflammatory changes in the metabolism, with increased free radical production by WBCs. Part of the excess of NE comes from augmented production. As above, there is a steady upward pressure on NE levels from up-regulation of DßH. But with aging, there also is a great decrease of the two most important ways of reducing NE, (i.e. exercise and REM sleep). This ever-increasing level of NE causes direct effects throughout the system. Some of this peripheral norepinephrine stimulates WBCs to produce Interleukin-1 and more inflammation. Some NE causes hormone shifts toward survival mode. Norepinephrine Metabolism During Exercise The physiology of the enzyme PNMT (Phenyl ethanolamine N Methyl Transferase) is extremely important to this process of converting norepinephrine to epinephrine. PNMT is found only in the brain, heart and lung. However, most of this enzyme is sequestered in the lower lobes of the lungs and circulation is markedly reduced to these areas during normal sedentary respiration. through PNMT, which is attached to cell membranes of

2 the lower lung tissue. During exercise, however, deep breathing opens alveoli in the lower lung, and circulation to this area improves dramatically. If the patient can be convinced to go running, the increased circulation to the bases of the lungs increases exposure of circulating norepinephrine to the enzyme PNMT. This allows NE to react with methyl group donors such as SAMe or ADMA in the basal segments of the lung. The methyl group donor reacts to transfer a methyl group to norepinephrine creating epinephrine. The epinephrine stimulates vasodilatation, broncho-dilation and increased ATP formation by the mitochondria. Classically, S-Adenosine Methionine is said to provide the methyl group required. It would appear that other methyl group donors can be substituted, however. Methyl groups are precious to our metabolism and are used to regenerate G-receptors and for conversion of NE with PNMT. The system protects methyl groups and trades them around within the system. Several donors such as Vitamins B12 and B6, Asymmetric Dimethyl Arginine, tetrahydrocannabinol and methylene blue, all can reduce the total load of norepinephrine by contributing methyl groups to the system. See below. The Dual Nervous System and Inflammatory Balance At this point we need to describe how the nervous system reflects the level of stress. For most people, the term nervous system means the Systemic nervous system, which runs on acetylcholine. The Systemic system starts with the cerebral cortex and includes the muscle control areas of the parietal cortex. The Systemic nervous system also includes all the sensory input nerves and apparatus. Muscle control neurons have long dendrites that are wrapped in a myelin sheath to keep them from shorting out along the way. The classic teaching is that the central nervous system sends signals as action potentials to the muscles, which react with appropriate muscle spasm. But what does the word send mean in this situation? Is the signal launched or in some way propelled? What makes the nerve impulse (action potential) propagate forward to the muscle? The Closed Circuit All higher animals have a dual nervous system. Like any other electric system, the Systemic nervous system must have a positive charge, a negative charge and a closed circuit. The positive charge is provided by acetylcholine, with a pka ~5.6. The negative charge that closes the circuit is provided by the Sympathetic nervous system, which is based on norepinephrine.

3 The Sympathetic system acts as a negative ground wire for the positive Systemic system. The Sympathetic nervous system is anchored in the limbic system and it carries the negative charge of norepinephrine, which has a pka of ~9.2. The difference between the two transmitters must come to the mid-point between ~5.6 and ~9.2. This point is a ph of 7.4. This of course, is the ph at which the Human metabolic system and most animal systems must operate. The voltage of the system can be quickly calculated: References give a conversion factor at 37.5 o C of 60mV/pH unit. 60mV x 3.6 pka units = 216mV This value, 216mV, is the voltage difference that runs the nervous systems in all vertebrate animals. An example that proves the point is the measurement made of the reaction curve of the mouse nachr (nicotinic acetylcholine receptor) where acetylcholine reacts directly with norepinephrine. The peak current of mouse muscle nachrs was reversibly decreased at both acidic and alkaline ph. This bell-shaped ph profile with a maximum at ph 7.4 had two apparent pka values of 5.6 and 9.2, which are the pka values for acetylcholine and norepinephrine. The Body is Charged by the Dual Nervous System Like a wire connected to a battery, the voltage of the sympathetic system is the same at the tip of the sympathetic nerves as at the center of the limbic system. The Sympathetic system is not insulated so it carries its electric charge all along its surface. There is a constant slow leak of norepinephrine, which gives vascular tone to the arterial system. Centrally, the Sympathetic nervous system is held apart from the Systemic acetylcholine system in a chain of ganglia on each side of the spinal column. From these ganglia, sympathetic nerves branch out to accompany every artery and arteriole to every part of the body. The systemic system, based on acetylcholine, goes to every muscle and every sensory unit. Internal organs have an equal dual system, but the acetylcholine is provided by the parasympathetic system. The system has a variable clock speed, up to cps, which is transmitted from the locus ceruleus and is pushed by the rate of production as norepinephrine is created (percolator coffeepot effect). The two nervous systems intertwine, and they re intimately associated within microns of each other, but never touch. There is a constant leak of acetylcholine at the neuromuscular junction, which

4 gives muscle tone. Acetylcholine molecules that reach the acetylcholine receptor and fit into it, stimulate muscle contraction and further energy release. Acetylcholine is quickly neutralized by acetyl-cholinesterase, which is tightly bound to the receptor. However, acetylcholine that does not reach a receptor is free to react chemically with norepinephrine. Life Force There is an electromagnetic field generated within living tissue that makes it alive. This has great importance for understanding the question of what it means to be alive. Rationale: The first figure in the panel shows a battery connected to two antennae, one charged positively and one charged negatively. Electromagnetic forces will exist between the two antennae. If this voltage were cycled 450 times per second (the clock speed of the brain), an electromagnetic field would be generated. Now substitute the Systemic nervous system for the positive antenna and the Sympathetic nervous system for the negative antenna. They are completely intertwined everywhere throughout the body. The two systems come within microns of each other everywhere throughout the system, but never touch. The force between the two systems is small, with a voltage difference of 216 mv. However, the distance between the positive and negative nets is also very small. The Energy of Life At the neuromuscular junction, and at other areas such as tear glands, the reaction of norepinephrine with acetylcholine releases energy that is fairly obvious. But the energy of life is released in every tissue of the body. At every point in every tissue, there is a positively charged systemic, acetylcholine nerve dendrite and a negatively charged, sympathetic norepinephrine nerve near-by. Sympathetic NE nerves are wrapped around the every arteriole or capillary. At every point there will be a charge gradient and voltage of 216 mv across the tissue.

5 This energy is what we feel to be alive! This charge would have a clock speed created by the locus ceruleus, based on stimulation and a multitude of environmental and hereditary factors as described above. The voltage would rise and fall in the peripheral tissue with the clock speed of the brain ( bursts per sec). There is a slow leak of acetylcholine that gives muscle tone. There is an equivalent, balancing leak of norepinephrine from the sympathetic system that gives vascular tone. The NE and Ach are drawn to each other and react without an enzyme, releasing energy and creating epinephrine. Any charged molecules in the peripheral tissues would line up and travel toward their opposite charge. Negatively charge molecules would move toward acetylcholine and positives would move toward norepinephrine. Charged molecules travel along these magnetic lines. This may be a clue to the apparent effectiveness of magnets, as therapy to disrupt inflammation. When a patient dies and the grid goes down, the patient s skin feels un-alive within a few minutes. While we are alive, there is a constant flow of electromagnetic energy at the clock speed of the brain, which vitalizes the tissue and sets the tone for all metabolism. This is the same reaction that occurs in the thalamus. This reaction occurs spontaneously during thought. The acetylcholine donates a methyl group to norepinephrine, which forms epinephrine. This releases energy and gives tone to the muscles and the vascular system. If there is an excess of acetylcholine, it will stimulate increased nitric oxide and vasodilatation. If there is an increase the amount of norepinephrine, it will cause vascular spasm and increased inflammation. See the sections to follow.

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