04/07/2009 - Articles

Nitric Oxide and Vascular Health - Article XV (Part 2 of 4)

By: Ed G. Lakatta, MD


In this, the second part of Dr Ed's article on reversing the atherosclerotic disease process in your arteries, the important role of nitric oxide (NO) in blood vessel dilatation is explained.

To read all the articles in the series, you can go to the mini-site: "Aging of Your Heart and Blood Vessels is Risky" by clicking here .

How Does Nitric Oxide Prevent Atherosclerosis and Promote Vascular Conditioning?

Nitric oxide (NO) is produced by healthy endothelial cells. The discovery of its function is possibly one of the most important in the history of cardiovascular medicine. In 1998 three Americans (Robert F. Furchgott, PhD, Louis J. Ignarro, PhD, and Ferid Murad, MD, PhD) were awarded the Nobel Prize for their independent discoveries concerning "nitric oxide" as a signaling molecule in the cardiovascular system. A signaling molecule is one which produces another substance, called a second messenger. Second messengers help in some way to carry a message from the outside of the cell to the inside.

When NO, the signaling molecule, enters a cell, it activates an enzyme called guanylate cyclase , which produces cyclic GMP, the second messenger. It's cyclic GMP that actually does the work of relaxing and dilating the blood vessels.


In addition to relaxing and dilating blood vessels, NO functions to prevent heart disease and strokes in several additional ways. It helps prevents atherosclerosis by preventing platelets and white blood cells from sticking to the vessel wall. NO also, under many conditions, reduces the production of free radicals, which can cause your vessels to age rapidly. Further, it suppresses abnormal growth of vascular muscle cells which causes thickening of the vessels.

Sex and Nitric Oxide

The discovery of how NO works has led to better sexual performance for many older men. If you think I threw this in just to wake you up, maybe I did, but nevertheless it's true. Insight into the function of NO brought about the development of Viagra, a medication for the treatment of impotence. Viagra, however, is specific for blood vessels in the penis because these vessels have a special form of guanylate cyclase and Viagra acts only on this form. It causes the smooth muscle cells in the blood vessels of the penis to relax and thus dilate.

Another drug in the same general class as Viagra, nitroglycerine, which is given for angina, has a similar action, causing blood vessel dilatation; however being non-specific it dilates multiple blood vessels in the body. At one time patients with impotence rubbed nitroglycerine paste on their penises to produce an erection. A systemic, or total-body reaction, often caused both partners to complain of a headache. NO produced by the healthy endothelium is directed only where needed.

'Catch 22' - Endothelial NO Protects the Endothelium but its Production in the Body Is Dependent On a Healthy Endothelium

The substance from which endothelium-derived NO is formed is an aminoacid known as L-arginine. Aminoacids are the building blocks of proteins. Essential aminoacids cannot be produced by the body and must be supplied in the diet. Non-essential aminoacids can be synthesized by the body and are thus not required as such in the diet. L-arginine is a semi-essential aminoacid. This means our bodies make some of this and we get additional amounts from the protein foods we eat.

Persons with healthy endothelial cells have sufficient L-arginine to produce required amounts of nitric oxide. Furthermore, scientific studies have shown that persons with healthy endothelial cells will not make additional nitric oxide if given dietary supplements of L-arginine.

Persons with unhealthy endothelium cells, however, cannot make adequate nitric oxide. The reason for this is that there is a modified amino acid circulating in the blood of people with, or at risk of, heart disease, called ADMA (asymmetric dimethylarginine) which opposes the action of L-arginine in the body and thus blocks and turns off the production of nitric oxide. Persons at high risk for heart attack and stroke cannot excrete ADMA and so have high levels of it in their blood. These persons will respond to supplements of L-arginine by producing nitric oxide. This is one rational for using this dietary supplement as an intervention for prevention of coronary heart disease.

Part Three of this article will provide you with a program to promote and maintain a healthy endothelium.

Dr. Ed is a physician/scientist, who is internationally recognized for studies that range from humans to molecules on how the heart and blood vessels work in health and disease as the body ages.


Created on: 06/02/2003
Reviewed on: 04/07/2009

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