Nitric oxide: what it is, how it is produced and physiological functions

Nitric oxide (NO) is a free radical nitrogen capable of oxidizing or reducing compounds with which it comes into contact. It is a powerful vasodilator commonly used in the inflammatory process against pathogens, viruses and cancer cells.
It is a gas formed by the union of a nitrogen atom bound to an oxygen atom that can be produced by endothelial cells. (cells that represent the inner lining of blood vessels, lymph vessels and the heart), but also from macrophages (a specific class of phagocytes, cells involved in immune defense).

During an inflammatory state, a number of reactions, including the release of histamine as a result of the rupture of mast cells (cells containing histamine and present in connective tissue), whose active presence is chain reactions that, among other things, stimulate the synthesis of nitric oxide (NOS) in production of nitric oxide.

nitric oxide synthetase (NOS), as just said, is a enzyme (actually an enzyme complex ) responsible for the production of nitric oxide , and 3 different types (isoforms) can be distinguished:

1. 1. Nitric oxide synthetases endothelial (eNOS), produces low levels of nitrogen oxide with primary function as a vasodilator
   2. Nitric oxide synthase neuronal (nNOS), produces low levels of nitric oxide with the main function of working as a neurotransmitter

Nitric oxide synthetase inducible (iNOS), produces high levels of nitric oxide with the main function of working in organic defense against pathogens

With regard to eNOS and nNOS – two dependent synthetases of nitric oxide and calcium, which are activated in the production of nitric oxide only when the concentration of calcium ions in the cell increases.
On the other hand, iNOS is always an active inducible synthetase, it is independent calcium and the synthesis of nitric oxide in this case is related to the amount of enzyme produced by the cell. This is typical of macrophages and is therefore activated in the presence of inflammatory conditions or bacterial aggression.

Vasodilation , which leads to the release of nitric oxide along with increased permeability of blood vessels, facilitates the leakage of fluids, leukocytes and proteins that leave the bloodstream and are involved in the management of the inflammatory process.
Thus, nitric oxide , despite being a potentially harmful element, performs a variety of physiological functions, including

• Relaxation of smooth muscles (also involved in vasodilation as a result of an inflammatory condition)
• Regulation of the cardiovascular system
• Platelet aggregation

Nitric oxide easily penetrates cell phone membranes and fluids and, in high concentrations, can alter cellular and enzymatic functions, cause DNA mutations and changes in the plasma membrane that cause cell death as a result apoptosis (cell suicide) due to interruption of its cycle.

At low levels, nitric oxide acts in exactly the opposite way, stimulating the action of HSP proteins (heat shock proteins) or heat shock proteins. These proteins, also called companion proteins, perform a number of fundamental functions, such as transposition of newly synthesized proteins to their destination, detecting denatured and / or damaged proteins, and attempting to “repair.” If this attempt fails, proteins HSPs transport damaged proteins to the proteosome, where they are digested and the amino acids that make up them are restored.

Nitric oxide has an almost local effect, so it cannot interact with anatomical regions, it also decomposes very quickly . Its half-life is only a few seconds, and immediately after that, nitric oxide binds to the heme group of hemoglobin present in red blood cells to form methemoglobin and, therefore, nitrites and nitrates are mainly eliminated by the kidneys.

Nitric oxide and its functions for athletes

The benefits of nitric oxide for athletes are potentially numerous, assuming it can rule out any possible side effect (even very serious) associated with a high presence and / or production, it is assumed that benefits may relate to hypertrophic process , improve blood flow to tissues by optimizing both muscle work and the subsequent recovery phase.

Although it is known primarily in the bodybuilding field, nitric oxide can be beneficial in a general sense in the field of sports, as increases the lumen of blood vessels. , and therefore facilitates the transport of blood tissue, improves any activity or exercise, allowing it to last longer or support more intense efforts.

Wanting to learn more about this product is paradoxical (as is often the case in bodybuilding), its use and the hypothesis about the real effectiveness of the supplements can even be counterproductive . One of the mechanisms for stimulating muscle growth, hypertrophy, is actually maintained by the presence of an acidic environment, a condition that will instead be less significant in the presence of nitric oxide, since the greater blood supply guaranteed by vasodilation will cause less onset of acidosis and faster and more efficient removal of lactic acid, which potentially reduces the hypertrophic effects of muscle acidity.

As a rule, strength and endurance parameters are improved . With an effect / production cycle, which is better explained below.

Nitric Oxide Supplements

Being a gas, it is easy to understand that its direct integration is technically impossible and, apart from the assumption that inhale mixtures fortified with nitric oxide (i.e., nitric oxide) in a hospital setting (which happens for specific clinical needs) or infuse it directly into tissues, also because (we remember) its action is local and non-systemic.

However, it is easy to find supplements that are officially marketed with names or through promotional methods that suggest that it is a nitric oxide supplement. In fact, these supplements mainly contain arginine, often in combination with other amino acids. Technically, therefore, they are additives of the amino acid arginine, which is the last precursor in the process of nitric oxide synthesis (the decomposition of L-arginine to citrulline causes the release of the nitric oxide molecule), in the intentions (and in the marketing promises) of the introduction of arginine to a greater extent will lead to more excretion nitric oxide.

However, the processes associated with the synthesis of nitric oxide are very different and complex and require a number of mediators to trigger their release. The simplification associated with taking the precursor leading to the release of nitric oxide would be similar to the fact that, being the precursor of testosterone with cholesterol, the possession / ingestion of food containing high concentrations of cholesterol induces more testosterone synthesis as a simple and direct consequence.

These supplements have been reported to contain other amino acids along with arginine, often citrulline, which can increase the availability of arginine to participate in nitric oxide synthesis.

Failure of these supplements is actually a positive element, as an increase in nitric oxide values ​​can cause, in addition to hypothetical benefits, real adverse effects caused, for example, by protein nitration ( as a result of the interaction of nitric oxide with free radicals and a series of cascading events), exposing only for example, in events such as heart attack or atherosclerosis.
Generally speaking, an oxidizing agent with a strong oxidative effect can cause effects similar to smoking, alcohol and ionizing radiation.

Therefore, can additives that increase the endogenous synthesis of nitric oxide be considered completely useless? Not really. Leaving aside only pure marketing, which tends to be artificially simplified, realizing that you need to involve people who are less able (or less eager) to understand the mechanisms of action, there is another aspect. In fact, it can be assumed that consumption of arginine during physical activity decreases the organic ability to cope with adequate nitric oxide production due to a trade-off in the levels of its precursor: arginine itself. This hypothesis is the only one that still leaves a question mark on two fronts:

• Process optimization hypothesis, starting with an integrator
• the hypothesis of the performance benefits associated with nitric oxide overproduction (and contextual, not secondary) by eliminating side effects

Medicines capable of increasing nitric oxide values ​​and further additive limits

Medicines can be identified next to the additives analyzed so far. which, in this case, without a shadow of a doubt, can increase the presence of nitric oxide. It is nitroglycerin, which many know for its fame as an explosive, but which instead finds use in the pharmacological field due to its ability to decompose slowly released nitric oxide. In this case, in order to spread to the muscle cells that surround the blood vessels, promoting relaxation and therefore vasodilation, in people suffering from a heart attack, there is a fundamental circumstance for which it represents a real life-saving operation.
Nitroglycerin , applied mainly locally, undergoes enzymatic decomposition with the release of nitric oxide and counteracts the reduced organic capacity of the vessels, inside which there are plaques, which, in addition to the impossibility of suitable vasodilation, further restricts the lumen of the vessels and causes suffering due to a decrease in the supply of oxygen to the tissues. p>

Nitroglycerin is not the only drug that regulates nitric oxide levels, the famous Viagra (whose active ingredient is sildenafil) affects the enzyme complex responsible for its production. In addition, the mechanisms underlying erection are precisely regulated by nitric oxide mediated relaxation of the smooth muscles of the corpus cavernosum and arterial vessels, followed by narrowing of the veins. It goes without saying that marketing around the aforementioned supplements will soon spread promises to improve sexual performance .

The presence of a drug, the functioning of which, for example, made it clear that it is completely different from what the supplement does, however, this should make us think: if the use of a precursor is sufficient and sufficient condition to trigger an increase in nitric oxide aimed at the process of vasodilation (the same consequence is required in the field of sports) why do arginine patients not use an arginine supplement, but a completely different molecule?

Then a second, more pressing problem arises: the use of nitroglycerin requires the presence of enzymes that, as a result of decomposition, allow the release of nitric oxide. These enzymes are more present at the venous level than at the arterial level and decrease further at the capillary level. It follows that even the hypothesis of pharmacological use for goals related to athletic performance, leaving aside the local and non-systemic effects of nitric oxide, will primarily affect venous circulation, therefore removal of catabolites fetus muscle more work than in the pumping phase.

However, even if we want to uncritically (and at this point paradoxically) admit that the use of arginine supplements, although sold as nitric oxide supplements, can not only increase synthesis but also benefit from the effects, it is necessary to assess the relationship between arginine from supplement and arginine in food .

On average, the presence of arginine in a supplement is 3 grams (see manufacturer’s recommended dosages, not content per tablet), equal to the amount found in 150 grams of beef or turkey meat or loga amount bresaola or lentils or chickpeas or many other commonly used foods. Therefore, it is difficult to assume that this may be an element deficiency in a normal diet, even of a vegan or vegetarian type, up to the need for integration.

Physiological induction of more nitric oxide production and actions that mimic its effects

There are physiological processes that can stimulate the release of nitric oxide, and actions that, while not affecting this parameter, actually create the same adaptations.

Consistency at high altitude

In relation to adaptations that athletes look for as an effect of nitric oxide (or are used as a cause). sales of supplements) may report vasodilation aimed at the desire to improve blood flow to muscle structures, control blood pressure values, facilitate the removal of blood atabolites, and improve muscle oxygen supply.
Remember a significant proportion of aerobic work is a sufficient condition for obtaining all of the above, also associated with the phenomenon of capillary regeneration, with a long-lasting and proven effect.

In fact, physical activity generally improves nitric oxide itself by stimulating the heart to respond to altered muscle oxygen demand, arterial endothelial cells release more to allow vasodilation. It is an effective process, but which is in adults and in the elderly under the influence of oxidative stress caused by free radicals tends to decrease in effectiveness.