Oxidul de azot

Nitric Oxide:

NO is essential to the everyday activities of many cells and tissues in the body. Therefore, any pathology of NO production in the body can lead to many diseases . Because of this, NO is also called a vital-poison, the right amount of NO production is essential for life, but too much or too little can be deadly poisonous. In most life-threatening diseases like hypertension, atherosclerosis,and diabetes.

One of the most important reactions discovered so far is the interaction of NO with certain proteins causing various enzymes to either be switched on or switched off.

Nitric Oxide (NO) is a very important signaling molecule that acts in many tissues to regulate a wide range of physiological processes. It was first discovered several years ago by a group that was attempting to identify the agent responsible for promoting blood vessel relaxation and the regulation of vascular tone. This particular agent was named endothelium-derived relaxing factor (EDRF), and was initially assumed to be a protein like most of the other signaling factors previously discovered. The discovery that EDRF was in fact nitric oxide, a small gaseous molecule, has led to many publications over the years. Scientists found that besides promoting blood vessel relaxation and the regulation of vascular tone, NO plays a key role in many biological processes including immune defense, neurotransmission, and the regulation of cell death (apoptosis). Since NO is such a very small molecule, it is able to diffuse rapidly across cell membrane and depending on the conditions, is able to travel several hundred microns. Nitric oxide is produced by enzymes known as nitric oxide syntheses (NOS).

Nitric Oxide Syntheses:

Nitric Oxide (NO) is produced by a group of enzymes called nitric oxide syntheses (NOS). These enzymes (present in body) convert the Arginine in Arginine alpha-Ketoglutarate (AKG) into citrulline, producing NO in the process. Oxygen and NADPH are necessary co-factors. The pure and simple science starts with the correct form of AKG.

There are three isoforms of NOS which have been named according to their activity.

1. Neuronal NOS (nNOS),
2. Endothelial NOS (eNOS), and
3. Inducible NOS (iNOS).

Scientists commonly refer to these enzymes by number so that
nNOS is known as NOS1,
iNOS is known as NOS2
eNOS is NOS3.
The 3 isoforms of NOS are the products of three different genes.

Although there are three names, these isoforms can be found in a variety of tissues and cell types working toward the same biological functions. nNOS & eNOS synthesizes nitric oxide in response to intracellular calcium levels. In other words, like all NOS isoforms, its activity is dependent on the binding of calmodulin. Increases in cellular calcium leads to increases in levels of calmodulin and the increased binding of calmodulin to eNOS and nNOS which then leads to an increase in NO production by these enzymes. The binding of calmodulin is required for the activity of all the NOS isoforms to convert Arginine alpha-Ketoglutarate to nitric oxide.


The pathophysiology of NO release

Huk & Malinski et al.(1997), have demonstrated in L-arginine- starved in vivo environments that the NO-producing enzyme can also donate an electron to its other substrate oxygen (O2) to form superoxide (O2–). When NO and O2– are produced simultaneously, in close proximity, they chemically react very quickly.The product of this reaction is called peroxynitrite (OONO–). In the presence of certain reactive centers,HOONO may undergo homolytic cleavage to a hydroxyl free radical (•OH) and nitrogen dioxide free radical (•NO2 ), or heterolytic cleavage to a nitronium cation (NO2+) and hydroxide anion (OH–). Three of these cleavage products (•OH,

•NO2 radicals and NO2+) are among the most reactive and most damaging species in biological systems and may be major contributors to the severe damage of the heart and brain. The low concentration of NO produced in the heart in atherosclerotic cardiovascular system is a prime cause of heart attack. Another serious disease associated with NO is septic shock, The affliction is usually initially caused by a bacterial toxin, which enters the blood circulation through incidental infections, wounds, and surgical procedures. Septic shock is due to the extensive release of NO. The immune system, attempting to fight infection, releases so much NO that the system goes out of control. Too high a concentration of NO dramatically decreases blood pressure, which is followed by failure of vital organ system, especially the liver, kidney and heart. During a heart attack, brain stroke, and any kind of condition which limits the supply of blood and O2 (ischemia) to an organ, a massive release of NO can be observed. Therefore, if blood flow can not be restored within several minutes,the NOS starts to produce superoxide in addition to NO. The simultaneous, proximal release of both NO and O2 may lead to serious, sometime irreversible damage especially in the brain or heart. The vital role of NO in the brain can change diametrically under pathological (disease) conditions. During a stroke, when the supply of blood to the brain is limited, a massive release of NO is observed 4–6 min after the onset of the stroke; NO concentration in the brain can reach as high as 2–4 μmol/L about 100 times higher than physiologic NO concentration. This highly nonphysiological NO concentration initiates a cascade of events leading to quasi-reversible or irreversible brain damage. Arnica is known to stimulate blood circulation and can raise blood pressure. In any cerebrovascular accident, the intra-cranial bleeding can be aggravated by Arnica leading to excessive extravasation of blood causing brain compression.