Nitric oxide (NO) is a gas which is found throughout the human body, in plants and in insects, which is important for the following functions:
Regulates blood vessel dilation.
Prevents blood clot formation in blood vessels.
Important in reproduction.
Dilates bronchi in the lungs.
Aids in bone formation.
Works in memory function.
Regulates insulin sensitivity.
Supports gastrointestinal relaxation.
NO is made from the amino acid, l-arginine, by the endothelial nitric oxide synthase (eNOS) enzyme: L-citrulline is a product of the process. NO is important in cardiovascular disease and endothelial dysfunction. NO is implicated in asthma, pulmonary hypertension, insulin resistance, erectile dysfunction and pre-eclampsia.
Most pharmaceutical anti-hypertensive medications are NO stimulants. Other treatments that may improve NO activity are statins, l-arginine, exercise and dietary changes. The pulsation of the blood against blood cell walls opens calcium channels of the endothelial cells (the inner lining of the bodies’ cavities) allowing calcium to enter the cells easily. The eNOS is calcium dependent and is stimulated by the increase in cellular calcium. NO is produced and diffuses into the area of the smooth muscles of walls of the blood vessels. The muscles relax and the blood flow increases. NO molecules are so small they can pass through cell walls without channels.
Inducible NOS (iNOS), which is 1000 times as strong as eNOS, is produced in inflammatory conditions and they can kill foreign organisms. Overproduction of iNOS is seen in septic shock, hemorrhagic shock, multiple sclerosis, neurodegenerative diseases, rheumatoid arthritis, ulcerative colitis and cancer.
NO plays an important role in regulating blood pressure and in preventing the development of atherosclerosis. Endothelial dysfunction is an early sign of atherosclerosis and predicts cardiovascular morbidity and mortality. Reduced NO activity is a sign of endothelial dysfunction. Oxidative stress is produced by reactive oxygen species, such as superoxides derived from xanthine oxidase, cyclooxygenase, and NAD(P)H oxidase. Endothelial dysfunction can cause hypertension.
NO modulates activity in the autonomic nervous system and maintains parasympathetic tone at the same time as suppressing a natural sympathetic activity. NO works in both the brain and in the peripheral nervous system.
NO works to control mitochondrial energy production and inhibits it during times of cellular stress to reduce oxygen usage. This reduces reactive oxygen species, preventing apoptosis (a natural form of cell death) from oxidative damage.
NO helps control insulin release. Diabetes mellitus and insulin resistance are seen with reduced NO activity and endothelial dysfunction.
NO is a gastrointestinal neurotransmitter that inhibits gastric acid production.
NO is the major mediator of the penile erection, increasing circulation to the penis. NO levels of the uterus increase during pregnancy and are decreased by labor. Reduced NO may play a part in pre-eclampsia., which is proceeded by endothelial dysfunction.
NO in the lungs causes dilation of the bronchi and increases the circulation. Pulmonary hypertension is associated with reduced pulmonary NO.
Bone contains NO where it promotes normal bone turnover and prevents osteoporosis. Inflammatory conditions, such as rheumatoid arthritis, can increase the levels of NO excessively, resulting in worsening of osteoporosis.
Treatments have been developed that release or donate NO, produce NO and/or protect NO from oxidative stress. Most of these treatments are pharmaceutical and include hydralazine, calcium channel blockers, beta blockers, ACE inhibitors and statins.
Non-pharmacologic stimulants of NO production include dietary sources and supplements of l-arginine. Test tube studies show that red wine from France increases eNOS and increased NO release. Black tea and cocoa, which contain antioxidant flavonoids, are treatments for endothelial dysfunction. Moderate and intense exercise has been shown to improve NO-related blood vessel dilation. A low calorie diet improves NO-related blood vessel dilation in obese and hypertensive patients. Vitamin C, vitamin E, omega-3 and folate may improve NO-dependent vasodilatation.
CONCLUSION: Nitric oxide is a “signaling molecule” important to many functions in the human body. Impaired function of this molecule results in endothelial dysfunction, cardiovascular disease, erectile dysfunction and osteoporosis.
There are other non-pharmaceutical approaches to this problem of NO deficiency. Supplements that are of benefit in NO deficiency include l-arginine, black tea, cocoa, flavonoids and, possibly, vitamin C, vitamin E, red wine, omega-3 and folic acid. Further clinical study needs to be done.
NOTE: Read about the clinical significance of endothelial dysfunction.
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