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Nitric oxide (NO), a soluble gas, is a physiological signaling molecule found in humans and many other vertebrate animals. Endothelial nitric oxide is produced in the lining of blood vessels, where it affects blood pressure by causing vasodilation, which is the widening of the blood vessels. It also influences arterial growth and immune responses. Decreased endothelial nitric oxide production or availability characterizes diseases such as atherosclerosis, where it contributes to high blood pressure, inflammation and sometimes blood clotting.
The entire circulatory system, including arteries, is lined with endothelium that controls blood pressure and serves as a selectively permeable barrier between the interior of blood vessels and the external environment. Nerves regulating the endothelium release the neurotransmitter acetylcholine. This sends a signal to the endothelial cells to make NO. The nitric oxide triggers vasodilation, relaxing the arterial wall and causing the blood pressure in the vessel to drop.
A central feature of endothelial dysfunction is the failure of blood vessels to dilate fully. When endothelial nitric oxide production or release is impaired, vasoconstriction follows as the blood vessel narrows. This in turn causes an increase in blood pressure. Without the regulating effects of nitric oxide, immune cells such as leukocytes proliferate, causing chronic inflammation. Platelets, which regulate blood coagulation, also proliferate, start adhering to the endothelium and form a blood clot that obstructs circulation.
Physiologically, there are many signals that induce endothelial nitric oxide production in healthy cells. The rate of blood passing through arteries and veins is believed to be the most important. Obesity complications, hypertension, high cholesterol levels, genetic diseases and a lack of exercise all contribute to endothelial dysfunction and to diminished production of nitric oxide. Exercise and reduced intake of saturated fats increases NO production. The amino acid arginine is the precursor molecule from which NO is made, so eating foods that are rich in arginine, such as beans and cold-water fish, might help to increase NO production.
Fats are prevented from sticking to the arterial wall by nitric oxide. With high levels of low-density lipoprotein in the bloodstream, cholesterol is carried to the walls of arteries. Reducing levels of nitric oxide permits the cholesterol there to adhere. Cholesterol adhering to the vessel walls is part of a chain reaction that causes damage to the endothelium, resulting in formation of the fibrous plaques that lead to atherosclerosis. It also causes decreased production of endothelial nitric oxide.
Nitric oxide, in the form of nitroglycerin, is used to treat angina. Nitroglycerin ingested to treat heart pain converts to NO in the body. It dilates the veins, decreasing the cardiac workload by reducing the amount of blood returned to the heart in each cardiac cycle. The heart then has less blood to pump.
Other drugs indirectly stimulate nitric oxide production and use. Penile erection is caused by signals from nitric oxide to dilate local blood vessels. Some erectile dysfunction drugs can increase the signaling by nitric oxide to penile blood vessels so that they function at a healthy, normal volume.
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