Nitric Oxide Explained

Posted by PredatorAdmin at 16:45 10/01/12

History of Nitric Oxide

The first signs of Nitric Oxide (NO) were detected by Furchgott and Zawadzki in 1980 when they showed that the relaxation of smooth muscle induced by Acetylcholine was dependent on the presence of the endothelium and provided evidence that relaxation was caused by the release of a labile humoral factor. This would become known as Endothelium-derived relaxing factor (EDRF). In 1986, Furchgott and Ignarro et al. developed the idea that EDRF may actually be NO, or a similar compound. Further investigation lead to the conclusion that EDRF is indeed, NO.


Sackner et al. (2005) states that one of the most fundamental benefits of active exercise is the release of nitric oxide (NO) into the circulation through activation of endothelial NO synthase (eNOS) owing to an increase in sheer stress to the endothelium.

Production pathway

NO is produced in the endothelial cells from the amino acid L-arginine, where it progresses to diffuse locally to the smooth muscle (Gilligan, 1994, Martin et al., 2001). The production of NO in the endothelium is due to the activation of endothelial nitric oxide synthase (eNOS). Stamler et al. (1994) and Kourembanas et al. (1993) describe that the amino acid L-arginine is converted enzymatically to NO due to oxidation of its guanidium nitrogen. The oxidation of L-arginine, due to the action of eNOS, leads to the production of NO and L-citrulline.


Once at the smooth muscle, NO increases intracellular levels of cyclic GMP (Guanosine monophosphate) and causes vascular relaxation, due to the reduction in available intracellular calcium. This free intracellular calcium is the dominant determent of vascular tone.


According to Ignarro (1989) an alternative hypothesis is that NO is formed and stored within vascular endothelial cells and that interaction of endothelium-dependent vasodilators with selective endothelial cell membrane receptors triggers NO exocytosis or secretion in a calcium- and oxygen-dependent manner. The requirement of calcium and oxygen for endothelium dependent relaxation might then be attributed to their necessity for NO formation.

Health Benefits of NO

It is well published in research that NO is a potent vasodilator, due to its effect on vascular smooth muscle. Through having such vasodilating properties, NO has been found to have many benefits in relation to health and disease. Although NO was discovered as a vasodilator, it mediates many of the protective functions of the endothelium.


NO has anti-atherosclerotic properties, which act upon the build-up of plaques that reduce the diameter of the lumen in blood vessels, which cause atherosclerosis. According to Ganz and Vita (2003) NO inhibits the production of tissue factor, which is a crucial molecule involved in the volume of accumulated atherosclerotic plaques that cause intravascular thrombosis. Adhesion of leukocytes and platelets to the endothelium causes endothelial dysfunction. Miyazaki et al (1999) have found that nitric oxide inhibits platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation.
 

Research has been found that shows NO to have indirect anti-inflammatory properties, due to its affect on vascular tone, platelet aggregation and leukocyte interactions with the endothelium. These anti-inflammatory properties appear mainly due to its suppression of nuclear factor – kb, which is the key transcriptional gene for inflammatory mediators (Sackner et al., 2005). Inflammation is an organism’s response to injury related to physical or chemical stimuli, which is involved in multiple pathologies such as arthritis, asthma, multiple sclerosis, colitis, inflammatory bowel diseases and atherosclerosis (Guzik et al., 2003). An inflammatory response acts to inactivate or destroy invading organisms, remove irritants, and prepare for tissue repair. The inflammatory response consists of specific immunological and non-specific immune reactions. Guzik et al. also found that NO may play regulatory roles at virtually every stage of the development of inflammation. NO also has the capacity to be utilised as a new treatment for inflammatory tissue injury. Research carried out by Grisham et al. (1999) outlines that NO may be used as a new therapeutic strategy for the treatment of inflammatory tissue injury.


The actions of NO have been found to be beneficial as part of pre-conditioning, in attempts to limit the harmful effects of ischemia, which is a restriction of blood supply. During pre-conditioning, NO is generated and acts to contribute the protection of the tissues involved. The protective effect of NO may be due to the dilation of microvessels or the inhibition of platelet adherence to endothelial cells (Bolli, 2001, Nandagopal et al., 2000, Vegh et al., 1992). Both actions contributing to an anti-ischaemic effect of preconditioning.


Transportation of blood solutes is an essential element of vascular efficiency. Research has been found which outlines that the presence of NO can enhance the transportation of blood glucose. Balon and Nadler (1997) have found that manipulation of the NO pathway in skeletal muscle could provide a novel approach to increasing glucose transport. Endothelial derived NO also serves to stimulate the uptake and metabolism of glucose in skeletal muscle. An investigation carried out by Young et al. (1997) found that NO acts to stimulate glucose metabolism in skeletal muscle, providing a novel mechanism that may function endogenously by the activation of nitric oxide synthase.


NO has also been found to play a beneficial role in the recovery and strengthening of tendons. Murrel (2006) found that all the isoforms of NOS, which is the enzyme that produces NO, are expressed during the process of tendon healing. Data collected by Murrel concluded that NO enhances extra-cellular matrix synthesis, leading to the recovering tendon becoming stronger than those not exposed to NO.


Vascular diseases, such as atherosclerosis, are much more common in individuals with diabetes. Diabetes causes a reduction in the availability of endothelium-derived NO, leading to the possibility of vascular disease. A study by Williams et al. (1996) found that there is clear abnormality of the NO pathway in patients with non-insulin-dependant diabetes mellitus. Williams also states that as well as the pathway abnormality, there is an increased inactivation of NO and an inability of the vascular muscle to respond to NO.


In addition to producing NO, the oxidation of L-arginine results in the production of Citrulline (CIT). CIT is an amino acid that has been found to be beneficial in protein synthesis, therefore playing a vital role in maintaining protein homeostasis (Moinard and Cynober, 2007). CIT also stands as a marker for renal and intestinal failure. The collective properties of CIT show its capacity for use in the field of clinical nutrition.


NO has properties that are highly beneficial in the treatment of cardiovascular diseases. The vasodilating qualities of NO give it the ability to increase coronary blood flow, which is very useful concerning cardiovascular diseases such as angina pectoris, heart infarct or coronary vasospasm (Martin et al., 2001).

NO and Building Muscle

It is well documented that NO has many physiological benefits, but which of these benefits can actually act to support and possibly increase muscle growth.


A key feature of NO is that it causes the muscle in your blood vessels to relax, causing vasodilation. This dilation of the blood vessels has the collective effect known as the ‘pump’. When you are ‘pumped’ your muscles will appear bigger and although these effects are temporary that doesn’t mean they are not beneficial in the long run. One only has to look at the infamous videos of seven-time Mr.Olympia winner Arnold Schwarzenegger in the documentary Pumping Iron to see how much he rated the ‘pump’.


As previously explained, NO acts to increase the volume of the lumen (which is the area in the centre of your blood vessels where blood passes through). As this area is increased, the volume of blood plasma passing through therefore increases. It is blood plasma that carries all your required nutrients to your muscles, including testosterone, amino acids and growth hormone. In turn, it can be theorised that NO leads to an elevated amount of muscle building substances being supplied to your working muscles (Prosser et al, 2009).


In addition to the nutrients stated above, the vaso-dilating properties of NO also increase the supply of oxygen to the working muscles. An increase in the amount of oxygen reaching your muscles will aid muscle growth as fatigue will be delayed and recovery enhanced (Shen et al, 2000).


The increased blood flow also allows quick delivery of readily available amino acids and nutrients from pre and post workout supplements straight to your working muscles, aiding recovery and therefore – growth!


The muscle building benefits of NO are clear, but the next step is actually managing to utilise these benefits, and the best way to do this is using supplementation.


Many dedicated bodybuilders precede their workouts with L-arginine, agmatine or Glycocarn based Nitric Oxide supplements in order to gain that valuable ‘pump’.
 

Recommended products

With many athletes and trainees looking for the ultimate muscle pump, nitric oxide supplements have become increasingly popular over the last few years. Let’s now take a look at four of the leading products available on the market.

iForce, Hemavol                                                                                  

Hemavol contains agmatine sulphate, which is seen by many as a superior compound compared to the L-arginine based supplements. You will feel the effects of Hemavol minutes after consumption, so take immediately prior to your workout. Hemavol also contains a huge dose of Citrulline Malate, which is a well proven NO precursor.

MuscleMeds, eNoxide

eNoxide does not use precursors to induce Nitric Oxide production such as L-Arginine and Citrulline, but actually delivers Nitric Oxide directly into the bloodstream.

Primordial Performance, Glycocarn Powder

GlycoCarn has been proven to increase the endothelial nitric oxide synthase and nitric oxide (NO) levels in human muscle. Human clinical trials have also demonstrated Glycocarn to increase nitric oxide (NO) levels from exercise stimulation. Proven by scientific research, GlycoCarn supplementation will produce great results.

MHP, NO Bomb

Another Gycocarn based supplement, NO Bomb has a range of pre and post workout benefits including massive muscle pumps, great energy and endurance, enhanced lactic acid removal, optimal recovery and fat loss promotion.

Author: David Rowse

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