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Role of Nitric Oxide
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Nitric oxide is a naturally
occurring molecule found in a variety of cell types and organ
systems. In the cardiovascular system, NO is an important
determinant of basal vascular tone, prevents platelet
activation, limits leukocyte adhesion to the endothelium, and
regulates myocardial contractility. NO may also play a role in
the pathogenesis of common cardiovascular disorders, including
hypotension accompanying shock states, essential hypertension,
and atherosclerosis.
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Nitric oxide has a
role in signal transduction. It was first identified as
endothelial-derived relaxing factor in blood vessels and as the
mediator of the bactericidal actions of macrophages. NO's role
as a neural messenger may be even more prominent. NO is a likely
transmitter of nonadrenergic, noncholinergic neurons.
Excess release of NO appears to account for a major portion of
neural damage following vascular stroke.
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Nitric
oxide is a cytotoxic agent of macrophages, a messenger molecule
of neurons, and a vasodilator produced by endothelial
cells. |
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Nitric
Oxide has been shown to be mediator of erectile function. NO
synthase, the synthetic enzyme for NO, was localized to rat
penile neurons innervating the corpora cavernosa and to neuronal
plexuses in the adventitial layer of penile arteries. Small
doses of NO synthase inhibitors abolished electrophysiologically
induced penile erections. These results establish NO as a
physiologic mediator of erectile function. |
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Both a
deficiency and an excess of NO are believed to be involved in
several pathophysiologic states. NO is a critical determinant of
basal vascular tone, and a deficiency of NO is associated with
hypertension. |
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Common
disorders that promote atherosclerosis, such as hypertension,
hyperlipidemia, smoking, and diabetes, are all associated with
abnormal endothelial function, one manifestation of which is a
comparative deficiency of bioactive NO. |
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A
deficiency of NO producing neurons in the gastrointestinal tract
is believed to be responsible for certain abnormalities in
gastrointestinal motility, such as Hirschsprung's disease,
achalasia, and chronic intestinal pseudo-obstruction. NO is also
believed to play an important role in gastric cytoprotection,
possibly by way of increased mucosal blood flow and the
modulation of gastric epithelial function. |
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Therapeutic
manipulation of NO levels¾by
providing the compound or by inhibiting its production¾has
profound effects in many clinical settings. For over 100 years,
congeners of NO, the nitrovasodilators, have been used to
provide exogenous NO to dysfunctional coronary arteries. These
agents, including nitroglycerin, isosorbide mononitrate and
dinitrate, and nitroprusside, promote vasodilation and platelet
inhibition and are metabolized to NO. |
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Given
the relative pulmonary selectivity of inhaled NO, this gas may
be useful at concentration of 10 to 40 ppm for the treatment of
persistent pulmonary hypertension of the newborn, the pulmonary
vasoconstriction that accompanies congenital diaphragmatic
hernia, primary pulmonary hypertension, and adult respiratory
distress syndrome. Higher concentration of inhaled NO may be
toxic, owing to the reaction of NO with oxygen to produce NO2. |
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