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For those that wish to know more about ours neurons problems :
http://www.tau.ac.il/~yosiba/noxide.html
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<TITLE>10. Nitric Oxide</TITLE>
<center><H1>10. Nitric Oxide</H1><BR>
<h1>A New Neurotransmitter</H5></center><HR>
Reprinted from <I>Medical Sciences Bulletin</I>, published by Pharmaceutical
Information Associates, Ltd.<BR>
<h5><i>this article was revised to fit better to the topics of this
course</h5></i> <HR><P>
<center><img src="LINES/rainbow2.gif"></center>
<h2>Nitric Oxide</h2><P>
Nitric oxide (NO) is a potent endogenous substance. it relaxes blood vessels, the lungs, the gut, and the genitourinary tract. It also plays an important role in immunologic defense and appears to be involved in
neurotransmission, insulin secretion, and even memory formation. Yet just a few years ago, NO was regarded as a desturbing compound, a contributor to smog, acid rain, and the ozone hole. One reason it took researchers so long to discover the important biologic functions of NO is that the compound is such a simple one. Neurotransmitters, by comparison, are much larger molecules stored in granules and released by specific stimuli, after which they move to a site of action and selectively bind a receptor. NO is a very small compound that is not stored but diffuses from its site of formation to its site of action (since it is both water- and lipid-soluble, it diffuses freely within tissues).
<P>
NO is one of the most potent substances released by the vascular endothelium; In the central nervous system (CNS), NO is a neuronal mediator that may be involved in neurotransmitter release and
even memory formation. Synthesis of NO in the CNS involves the same
pathways and the same enzyme as in the endothelium (NO synthase, with the
same cofactor requirements); however, NO formation in the CNS can be
triggered by stimulation of the glutamate receptor. Glutamate is an excitatory
neurotransmitter implicated in brain damage after cerebral ischemia and stroke. It now appears that stimulation of the glutamate receptor during ischemic causes a prolonged release of NO, with subsequent tissue damage. Thus NO in the brain is both beneficial (protecting, enhancing, and mediating the activity of neurons) and toxic (indiscriminately destroying neurons). <P>
In the peripheral nervous system, NO functions as a transmitter. It is found in nerves of the gastrointestinal (GI) and urogenital systems -- the so-called nitrogenic neurons -- where it is involved in GI peristalsis and penile erection. NO may also be involved in the release of insulin; excess NO may contribute to the destruction of b cells during the development of type I diabetes. <P>
NO plays an important role in immune defense. Activation of the immune
system results in the induction of macrophage NO synthase, which generates
large amounts of NO from L-arginine. When a macrophage encounters a
pathogen, it engulfs the organism and kills it with a shower of NO. The NO
causes massive oxidative damage via the production of oxygen, copper, iron, and hydroxyl radicals. Reactions between molecular oxygen and NO lead to the formation of strong oxidants (nitrogen dioxide and peroxy nitrites) that are even more toxic than NO itself. In some cases, this immunologic defense escalates until it reaches levels that are toxic to the host, with severe oxidative damage, hypotension, and shock. (Ariggard E. <I>Lancet</I>. 1994; <B>343</B>: 1199-1206.)<P>
<center><img src="LINES/rainbow2.gif"></center>
<H2>Nitric Oxide in Clinical Medicine</H2>
NO is being used therapeutically to treat certain diseases characterized by NO
insufficiency, including hypertension, angina, and impotence. There is evidence
that the L-arginine/NO system is defective in patients with hypertension and
possibly angina. NO has actually been used for angina for more than a century,
in the form of nitroglycerin. Only recently have researchers determined that it is
the NO released by nitroglycerin (NG) in the vascular wall that is responsible for the activity of NG. Inhaled NO has also proved effective for pulmonary
hypertension, common in neonatal and adult res-piratory distress syndrome and also after cardiopulmonary bypass surgery. NO gas in low concentrations (50-80 ppm) causes selective pulmonary vasodilation and improves arterial oxygenation without causing systemic vasodilation. In addi-tion, NO may have
bronchodilator activity. As it is a physiologic mediator of penile erection, NO (as NG) has been used for impotence. Application of NG to the penises of impo-tent men causes erection (but headache in sexual partners).<P>
<center><img src="LINES/rainbow2.gif"></center>
<H2>Nitroglycerin (NO2) for Preterm Labor</H2>
Prematurity is the most common cause of neonatal morbidity and mortality and
of long-term disability. Premature labor is generally treated with agents that have little effect on overall outcome, and strong side effects,
including death.<P>
"NG patch therapy could make a major contribution to the management of
preterm labor," said the investigators. "The rapid and effective action obtained
with the NG patch, its simplicity of administration, and safety suggest that a
prospective randomized comparison of NG with established therapy or placebo
should now be done." (Lees C et al. <I>Lancet</I>. 1994; <B>343</B>: 1325-1326.)
<P><center><img src="LINES/rainbow2.gif"></center><P>
<HR><h3><center>
<a href="sleep.html">Now it's time to move on to the next topic</a><br> or <a
href="intro.html">return to introduction page </a><hr><P>
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