- 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.
- 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.
- Nitric oxide is a cytotoxic agent of macrophages, a messenger molecule of neurons, and a vasodilator produced by endothelial cells.
- 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.
- 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.
- 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.
- 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.
- Therapeutic manipulation of NO levels, by providing the compound or by inhibiting its production,has 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.
- 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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