Nitric Oxide Everywhere

Nitric oxide (NO) is everywhere you look, assuming you're looking at changes in human biochemistry with aging, and the resultant degenerations and diseases of the body. I ran across one example not too long ago: nitric oxide is a part of the control mechanism for blood vessel dilation (vasodilation), located in the blood vessel lining, or endothelium, amongst other things. We know that a range of age-related conditions are related to degradation in the flexibility of blood vessels, and it seems this has more to do with damage to the control mechanisms, rather than incapacity of the tissue:

Endothelial dysfunction, often demonstrated by the loss of the endothelial cell’s ability to cause vasodilation in response to appropriate stimuli, is one of the earliest events in the development of atherosclerosis. This has led to intense investigation of the factors affecting both the production and the degradation of NO, the endothelium-derived relaxing factor and a primary mediator of endothelial function. Reactive oxygen species (ROS), particularly superoxide anion, are well known to inhibit NO, and therefore the mechanisms by which endothelium regulates production of ROS are also of high interest. In this issue of The American Journal of Pathology, Zhang et al demonstrate regulation of such events by a mitochondria-specific thioredoxin, which reduces oxidative stress and increases NO bioavailability, thus preserving vascular endothelial cell function and preventing atherosclerosis development.

Another good reason to damp down the production of reactive oxygen species is the way they damage mitochondrial DNA, leading to even more ROS being produced and exported into the body at large:

Cholesterols, such as low-density lipoproteins (LDL) are used everywhere in the body and travel widely. If ROS reacts with nearby LDL - and there will always be nearby LDL - to form damaged, oxidized cholesterol, that damaged cholesterol can then be incorporated into and further damage biochemical processes throughout the body. For example, its effects on our arteries is well known. In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease.

The body is a fascinating, complex, roiling sea of mechanisms and chemicals, many of which have evolved into use in multiple mechanisms and delicate balances between too much and too little. Nitric oxide seems to be important to stem cell activity, for example:

In the body, nitric oxide occurs naturally. It helps the repair cells move out of the bone marrow where they are made, and it opens blood vessels and improves the uptake of oxygen.


"We went on to show that actually what's happening is nitric oxide is affecting the skeleton, or scaffold of the cell, and by adding nitric oxide we're able to rearrange the scaffold," Segal said. "When we rearrange the scaffold, the cells are able to migrate. The benefit of this is that when cells have improved movement they are able to repair the endothelium (the lining of the blood vessels) better and perhaps prevent atherosclerosis."

Moving on, calorie restricted mice produce more nitric oxide - one of many pieces of the puzzle surrounding the mechanisms for the benefits to health and longevity provided by calorie restriction.

The results showed that mice that were fed 30% to 40% fewer calories produced more nitric oxide than those who followed an unrestricted diet. Calorie restriction also caused the mice to increase production of another chemical messenger that stimulated production of new mitochondria (the main energy source in cells) and increased oxygen consumption and expression of a protein previously shown to play a role in calorie restriction's effect on life span. These beneficial effects of calorie restriction were not found in mice that lacked the enzyme necessary to synthesize nitric oxide. Therefore, researchers say the findings suggest that nitric oxide may play a critical role in calorie restriction's effect on longevity.

Lastly, for this selection at least, suggestions that nitric oxide - like most chemicals in the body - isn't always a good thing:

An enzyme [iNOS] that triggers the production of nitric oxide (NO) - a gas that helps immune cells fight off invading pathogens - accelerates the formation of brain lesions in Alzheimer's-prone mice ... For nearly a decade, researchers have known that iNOS was present in the brain lesions of patients with Alzheimer's disease, but nobody had addressed whether its presence was making the disease worse. Nathan and colleagues now show that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice.

It all depends on context and circumstance - but a far greater level of understanding of our biochemistry will certainly lead to better ways to extend and improve health and longevity.

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I'm curious as to the correlation between hair loss and sleep apnea due to reduced levels of NO due to compromised upper respiratory tract and the degenerative nature of ongoing hypoxia in the vasculature. Does anyone have any information on this theory?

Posted by: DMG at March 6th, 2008 10:22 AM
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