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The Role of Nitric Oxide

 

An Educational Email:

Learn how Nitric Oxide was discovered as a Miracle Molecule for Human Health

 

"The Time is Always Now."

 

 

Nobel Prize® medal - registered trademark of the Nobel Foundation

The Nobel Prize in Physiology or Medicine 1998

          

 

 

 

The Nobel Laureates

THE CARDIOVASCULAR CURE

Nitric Oxide (NO)/Endothelium-Derived Relaxing Factor’s (EDRF)* Contribution to Cardiovascular Health

THE NOBEL LAUREATES** won their prize for discovering that NO is a po­tent relaxer of blood vessels. But since this landmark finding, we have learned much more about how NO contributes to cardiovascu­lar health. We have also learned how to improve the production of this lifesaving molecule through nutrition and lifestyle changes. 

Based on the work of many research groups, including my own, we now know that when someone has heart disease or risk factors for heart disease, their endothelium is impaired. When the endothe­lium is not healthy, the vessel constricts and, over time, the vessel wall thickens. Blood cells are more likely to stick to the vessel, and this accumulation may lead to the formation of a blood clot or the development of atherosclerotic plaque. 

However, when the endothelium is healthy, it releases NO, which relaxes the blood vessels, prevents cells from sticking to the vessel wall, and prevents the vessel wall from thickening. 

A healthy endothelium is like Teflon, a nonstick surface that en­hances the flow of blood. By contrast, an unhealthy endothelium is like Velcro, with white blood cells and platelets sticking to it. To­gether, NO and its sister molecule prostacyclin act together to main­tain the vessel in a relaxed state and to prevent the development of blood clots and plaque. 

What exactly does NO do for your blood vessels?

NO opens blood vessels and keeps them relaxed. To keep your cir­culatory system as healthy as possible, you will want your blood ves­sels to be as relaxed and pliable as possible.  NO is the strongest natural relaxant of blood vessels. By causing blood vessels to open up, NO increases blood flow through them. As a cardiologist I have several vasodilating drugs that I can administer to my patients. I use these drugs to improve blood flow and to lower blood pressure. But by ensuring that your body makes NO on its own, you have a natural vasodilator right in your own body. Like nitroglycerin, NO acts on the blood vessels immediately. 

NO prevents atherosclerosis. NO is a natural substance that pro­tects us from hardening of the arteries. It does this by preventing platelets (particles in the blood that form blood clots) and white blood cells from sticking to the vessel wall. NO also reduces the pro­duction of free radicals, which can cause your vessels to age rapidly. 

NO also suppresses the abnormal growth of vascular muscle cells, which can thicken the vessel. All of these processes-the sticking of blood cells to the vessel, the production of free radicals, and abnormal cell growth-contribute to atherosclerosis.  By halting these processes, endothelium-made NO is your body's strongest self-d­efense against heart attack and stroke. NO can prevent hardening of the arteries and even reverse it. This process may take some time and is one of the long-term benefits of NO. 

The last few years have been exciting for me and for other scientists working in this area of vascular medicine. We have uncovered many secrets of the body and the blood vessels. However, it is even more gratifying for me to use these secrets to enhance vessel health. I believe that it is important for people to learn how to enhance the eating power within-and to benefit from the body's natural def­ense against heart attack and stroke.  

Can NO help you? The answer is yes-by helping to keep your ves­sels relaxed and open and by preventing atherosclerosis. It is never too late to learn about the power of NO. I have seen people with very unhealthy blood vessels become more healthy. The endothelium can be repaired. Atherosclerosis can be reversed. 

When the lining of the blood vessels in healthy cells don't stick, clots don't form, arteries don't harden, and you won't die of a heart attack or stroke. The cardiovascular cure is a healthy endothelium.  It is certainly promising news for all of us. 

____________________________

This Article was written by John P. Cooke, M. D. PH. D.  It is from his book The Cardiovascular Cure, Page 12 and 13. The renown Dr. Cooke is the head of Stanford Medical School’s Vascular Unit.  Dr. Cooke is among the foremost authorities on Cardiovascular Health. 

* Endothelium-derived relaxing factor (EDRF) is produced and released by the endothelium that results in smooth muscle relaxation.

 ____________________________

 **The winners of the 1998 Nobel Prize for Medicine were Robert F. Furchgott Pharmacologist, Louis J. Ignarro Ph.D and Ferid Murad M.D.-Ph.D.

Now you can see and hear these Nobel Laureates discuss the Miracle Molecule, Nitric Oxide and its role in Human Health. You certainly will enjoy the video done by the University of Texas Houston, Science Health Center on The Discovery of the Effects of Nitric Oxide on the Circulatory System.

I highly recommend that you view the videos done by The American Health Journal's in their interview with the Nobel Prize winner Dr. Louis Ignarro. Just click here to watch Part One and Part Two. If your interest is peaked and it should be, it is time to order Cardio Cocktail,

Bob Fox

Press Release

NOBELFÖRSAMLINGEN KAROLINSKA INSTITUTET
THE NOBEL ASSEMBLY AT KAROLINSKA INSTITUTET

October 12, 1998

The Nobel Assembly at Karolinska Institutet has today decided to award the Nobel Prize in Physiology or Medicine for 1998 jointly to: Robert F. Furchgott, Louis J. Ignarro and Ferid Murad
for their discoveries concerning "nitric oxide as a signaling molecule in the cardiovascular system".

Summary

Nitric oxide (NO) is a gas that transmits signals in the organism. Signal transmission by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell represents an entirely new principle for signalling in biological systems. The discoverers of NO as a signal molecule are awarded this year's Nobel Prize.

Robert F Furchgott, pharmacologist in New York, studied the effect of drugs on blood vessels but often achieved contradictory results. The same drug sometimes caused a contraction and at other occasions a dilatation. Furchgott wondered if the variation could depend on whether the surface cells (the endothelium) inside the blood vessels were intact or damaged. In 1980, he demonstrated in an ingenious experiment that acetylcholine dilated blood vessels only if the endothelium was intact. He concluded that blood vessels are dilated because the endothelial cells produce an unknown signal molecule that makes vascular smooth muscle cells relax. He called this signal molecule EDRF, the endothelium-derived relaxing factor, and his findings led to a quest to identify the factor.

Ferid Murad, MD and pharmacologist now in Houston, analyzed how nitroglycerin and related vasodilating compounds act and discovered in 1977 that they release nitric oxide, which relaxes smooth muscle cells. He was fascinated by the concept that a gas could regulate important cellular functions and speculated that endogenous factors such as hormones might also act through NO. However, there was no experimental evidence to support this idea at the time.

Louis J Ignarro, pharmacologist in Los Angeles, participated in the quest for EDRF's chemical nature. He performed a brilliant series of analyses and concluded in 1986, together with and independently of Robert Furchgott, that EDRF was identical to NO. The problem was solved and Furchgott's endothelial factor identified.

When Furchgott and Ignarro presented their conclusions at a conference in July, 1986, it elicited an avalanche of research activities in many different laboratories around the world. This was the first discovery that a gas can act as a signal molecule in the organism.

Background

Nitric oxide protects the heart, stimulates the brain, kills bacteria, etc.
It was a sensation that this simple, common air pollutant, which is formed when nitrogen burns, for instance in automobile exhaust fumes, could exert important functions in the organism. It was particularly surprising since NO is totally different from any other known signal molecule and so unstable that it is converted to nitrate and nitrite within 10 seconds. NO was known to be produced in bacteria but this simple molecule was not expected to be important in higher animals such as mammals.

Further research results rapidly confirmed that NO is a signal molecule of key importance for the cardiovascular system and it was also found to exert a series of other functions. We know today that NO acts as a signal molecule in the nervous system, as a weapon against infections, as a regulator of blood pressure and as a gatekeeper of blood flow to different organs. NO is present in most living creatures and made by many different types of cells.

When NO is produced by the innermost cell layer of the arteries, the endothelium, it rapidly spreads through the cell membranes to the underlying muscle cells. Their contraction is turned off by NO, resulting in a dilatation of the arteries. In this way, NO controls the blood pressure and its distribution. It also prevents the formation of thrombi.

When NO is formed in nerve cells, it spreads rapidly in all directions, activating all cells in the vicinity. This can modulate many functions, from behavior to gastrointestinal motility.

When NO is produced in white blood cells (such as macrophages), huge quantities are achieved and become toxic to invading bacteria and parasites.

Importance in medicine today and tomorrow:

Heart: In atherosclerosis, the endothelium has a reduced capacity to produce NO. However, NO can be furnished by treatment with nitroglycerin. Large efforts in drug discovery are currently aimed at generating more powerful and selective cardiac drugs based on the new knowledge of NO as a signal molecule.

Shock: Bacterial infections can lead to sepsis and circulatory shock. In this situation, NO plays a harmful role. White blood cells react to bacterial products by releasing enormous amounts of NO that dilate the blood vessels. The blood pressure drops and the patient may become unconscious. In this situation, inhibitors of NO synthesis may be useful in intensive care treatment.

Lungs: Intensive care patients can be treated by inhalation of NO gas. This has provided good results and even saved lives. For instance, NO gas has been used to reduce dangerously high blood pressure in the lungs of infants. But the dosage is critical since the gas can be toxic at high concentrations.

Cancer: White blood cells use NO not only to kill infectious agents such as bacteria, fungi and parasites, but also to defend the host against tumors. Scientists are currently testing whether NO can be used to stop the growth of tumors since this gas can induce programmed cell death, apoptosis.

Impotence: NO can initiate erection of the penis by dilating the blood vessels to the erectile bodies. This knowledge has already led to the development of new drugs against impotence.

Diagnostic analyses: Inflammatory diseases can be revealed by analysing the production of NO from e.g. lungs and intestines. This is used for diagnosing asthma, colitis, and other diseases.

NO is important for the olfactory sense and our capacity to recognise different scents. It may even be important for our memory.

Nitroglycerin
Alfred Nobel invented dynamite, a product in which the explosion-prone nitroglycerin is curbed by being absorbed in kieselguhr, a porous soil rich in shells of diatoms. When Nobel was taken ill with heart disease, his doctor prescribed nitroglycerin. Nobel refused to take it, knowing that it caused headache and ruling out that it could eliminate chest pain. In a letter, Nobel wrote: It is ironical that I am now ordered by my physician to eat nitroglycerin. It has been known since last century that the explosive, nitroglycerin, has beneficial effects against chest pain. However, it would take 100 years until it was clarified that nitroglycerin acts by releasing NO gas.