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Your Blood Vessels and NO (and Why You Need to Know about Them)
This is a story about the health of your blood vessels. If you are like most people, you have probably given some thought to the health of your heart, but not the 100,000 miles of blood vessels that run throughout your body. Wherever blood flows in your body, it flows through blood vessels.
Blood vessels have been given short shrift mainly because people think that they are nothing more than passive pipes. But we now know that they are much more important than anyone ever realized.
Your blood vessels are dynamic, living tissue just like any other organ in your body. And just like every other organ, they perform a vital function: in this case, controlling blood flow from one moment to the next. Every 60 seconds, your vessels are responsible for distributing five quarts of life-sustaining blood to your body. Just think, five quarts every minute, 1,800 gallons every day, a virtual river of life.
Composed of living cells, blood is alive. And like all living things, blood has its own complex functions. It carries the oxygen and nutrients your tissues need to survive. It removes the waste products of cellular metabolism, distributing these to the liver or kidney where the waste products can be excreted. Blood carries hormones from the brain and other glands to distant parts of the body where these hormones are needed for the growth and function of each organ. When you cut yourself, blood has the ability to clot and stop the bleeding. And when you lose blood, your body has the ability to make new blood, replacing what's been lost. Blood carries white blood cells, your body's majordefense against infection. White blood cells course through all of the blood vessels, constantly patrolling for foreign invaders. If you think about it, blood is the unifying force within the body, both a link between distant parts and an intricate system of transportation that provides fuel, disposes of waste, and carries disease-fighting cells.
And all of this happens within the blood vessels.
As the conduit, blood vessels play a role in the ability of the blood to do its job. Blood vessels can control their own diameter and control the flow of blood from one moment to the next. They can open up to increase the flow of blood to where it is needed (such as to the muscles during exercise or to the pelvis during sexual intercourse). Blood vessels can also reduce the flow of blood to an area of the body. The blood vessels to the skin constrict or shut down completely when blood must be diverted (which is why a person may become pale with fear when blood is diverted from the skin to the muscles, heart, and brain where it is needed for fight or flight). Blood vessels can do this because their walls are made of muscle, similar to that of the heart muscle. This muscle responds to nervous impulses from the brain, to changes in pressure within the vessel, and to substances made by the endothelium, the inner lining of the blood vessel.
Blood vessels are always active and constantly in motion as they respond to the rhythms of the body: the heart, the flow of blood, signals from the brain, and signals from tissues of the body that need more blood. Like so many other parts of the body, blood vessels do their job without our conscious knowledge.
The small and large blood vessels perform different roles. The smaller vessels contract to restrict blood flow and dilate to increase it. They direct the flow of blood where it is needed. On the other hand, the larger vessels do not contract or dilate very much on their own, but instead respond to the beat of the heart. They expand with each beat, much as the inner tube of a tire expands when it is filled with air. When the heart relaxes between beats, the walls of the great vessels (the aorta, which carries blood from the heart to the rest of the body, and the pulmonary artery, which carries blood to the lungs) rebound, giving the blood an extra push forward, maintaining blood flow until the heart pumps again. (When you take your pulse, you are actually measuring the wave of energy that passes through the blood from the beating heart, expanding the vessels as the wave passes through.)
It is this dance between the heart and the great vessels that makes a smooth and efficient circulation system. To do their job properly--keeping pace with the heart, expanding and rebounding--vessels need to be pliable and elastic. You want your vessels to be as resilient as possible.
The problem is that--due to many factors, such as aging, genetics, poor diet, smoking, and sedentary lifestyle--the elasticity and flexibility of your vessels can become compromised. When vessels are the opposite of pliable and elastic, they are stiff and fixed in place like a pipe. When vessels are stiff, they can't comply with the beat of the heart and the waves of life-giving energy. When the heart pumps blood into stiff arteries, the heart must work harder. It takes more energy to pump blood through stiff vessels.
Although the smaller vessels do not harden like the larger ones, they can also become damaged and function poorly. Poor diet, lack of exercise, and risk factors such as aging, high blood pressure, high blood sugar, high cholesterol, and smoking all impair the ability of the smaller vessels to relax. The vessel wall becomes thicker and the bore of the vessels becomes smaller. The vessels tend to constrict rather than dilate and it is more difficult for blood to flow through them. Accordingly, to get the same amount of blood flow through these vessels, the heart has to pump harder. As a result, blood pressure rises.
For hundreds of years, we've known that blood pressure is a measure of the blood circulating through the body. It is determined by the amount of blood flow and the blood vessels' resistance to that blood flow. The pumping of the heart establishes the amount of blood flow. When the heart beats faster or contracts more vigorously, blood flow increases. The health of the blood vessels determines the resistance. When the vessels are relaxed and flexible, resistance is low. In about 90 percent of people with high blood pressure, blood pressure increases because the vessels are not relaxed or have thickened.
You are probably familiar with the way blood pressure is measured. The measurement is represented by two numbers, top and bottom. The top number is the systolic pressure, the pressure in the vessels at the time the heart beats and pumps blood into the arteries. The bottom number, or diastolic pressure, is a measurement taken when the heart is resting in between beats. The normal blood pressure reading for an adult is 140/80; anything over these numbers is considered elevated.
In my opinion, the lower your blood pressure, the better. Obviously, if your blood pressure is too low, you will faint. But I tell my patients that their blood pressure should be just high enough to keep them from falling over. Even if your blood pressure is as low as 90/60 but you can stand without trouble, this is healthy and, in the long run, better for your heart and vessels.
To understand the difference between arteries that are stiff and those that are compliant, think about the difference between a thick and thin balloon. It is difficult to blow air into a thick-walled balloon. Expanding a thick-walled balloon takes much more effort than expanding a thin one, and the thick-walled balloon doesn't recoil very far once it is stretched. Like the thick-walled balloon, arteries that have hardened take much more effort to expand--and that makes it more difficult for the heart to pump blood into them. When blood is pumped into vessels that are not compliant, blood pressure rises faster and higher. The vessels can't expand to accommodate the rush of blood. On the other hand, the thin-walled balloon expands, stretches, and recoils with ease. It should be obvious then that, to maintain cardiovascular health, we want our vessels to be pliable like the thin-walled balloon. As you'll find out, it is possible to return your blood vessels to their youthful state.
The Lining of the Blood Vessel--the Endothelium
if you were to look at the outside of a blood vessel, it would appear enmeshed and attached to surrounding tissue, almost as though it had a myriad of threads circling it. The inside of a blood vessel is different, made up of smooth tissue, the easier to facilitate the flow of blood.
A closer look inside a blood vessel takes us to the endothelium, the innermost layer of tissue that lines the blood vessel. If you were to look at a cross section of an artery, the endothelium would be the inner surface. It would be similar to looking into a garden hose: the inside of the hose is lined by a smooth surface that is like the endothelium.
All blood vessels are lined with a carpet of endothelial cells. The blood vessels in your skin, brain, heart, and all of your organs are lined with this film of tissue. Only one cell layer thick, the endothelium seems almost immaterial, so thin that it cannot be seen by the naked eye. Yet it is a fascinating, versatile, and vital part of our anatomy. It could even be considered the largest organ in our body. Because this almost invisible veil of tissue lines all blood vessels, and because we have about 100,000 miles of blood vessels, the endothelium has the surface area of eight tennis courts. Incredibly, if all of the endothelial cells in the body were lumped together, they would weigh as much as the liver.
For many years, researchers believed that the endothelium was nothing more than an inert layer of cells, a simple barrier between blood and the smooth muscle wall of the vessel. Nevertheless, the process through which this "barrier" worked fascinated physiologists for many years--ever since it was found that certain substances seemed to pass through it, whereas others could not. It acted as a selective filter for the vessel wall. Eventually, scientists suspected that the endothelium was more than just "wallpaper," as it had been called.
In 1966, Nobel laureate Lord Howard Walter Florey, honored in 1945 for discovering penicillin, predicted that we would eventually see "a rich harvest of new knowledge about the cells which stand between the blood and lymph streams and the cells of the tissue." No longer would endothelial cells be regarded as "little more than a sheet of nucleated cellophane," Florey wrote.1
Florey's words were prophetic. We now know that the endothelium exerts tremendous control over blood flow. First, its prime location plays a role. Because the endothelium is the innermost lining of the blood vessel, it has direct contact with blood and, as such, serves as an interface between the blood and the vessel wall. That relationship is everything, providing a clue to many details about the endothelium's job.
One detail in particular proved interesting to scientists studying the endothelium in the 1950s and was noted by Lord Florey in the 1960s: there was something special about endothelial cells since they permitted certain substances to pass through their barrier. Lord Florey even hinted in 1966 that "endothelial permeability may be of importance in elucidating the initial phases of the development of atherosclerosis."
But the endothelium is much more than a highly selective filter. We now know that this delicate tissue, only one cell layer in thickness, is a dynamic factory, producing a myriad of substances that maintain vessel health. It is, in essence, a silver lining--since when it's healthy, it produces its own forms of heart medicine.2
A Major Advance in Cardiovascular Medicine--the Discovery of NO/EDRF
this new chapter in cardiovascular medicine began with dynamite. In 1860, Alfred Nobel successfully made nitroglycerin explode. Six years later, he invented dynamite, using nitroglycerin as the active ingredient. Even then, in Alfred Nobel's time, scientists knew that small amounts of nitroglycerin could be given to relieve angina, but they didn't know how nitroglycerin worked. Somehow small doses of the explosive relaxed the muscles of the blood vessels, enabling the vessels to dilate. In people who had angina, nitroglycerin relieved the pain of the heart, which was starved of oxygen and nutrients.
Late in life, Alfred Nobel himself developed angina and took nitroglycerin for pain relief. "Isn't it the irony of fate that I have been prescribed nitroglycerin, to be taken internally," Nobel wrote to a colleague before he died of a heart attack in 1896. "They call it Trinitrin, so as not to scare the chemist and the public."3
But it wasn't until the 1970s that scientists began to uncover the mystery of how nitroglycerin worked. It was Dr. Ferid Murad, at the University of Virginia and later at Stanford University, who made the great leap forward in solving this medical puzzle.
Early on in Dr. Murad's career he became interested in how cells signal to one another. "I decided to work with cyclic GMP [guanosine monophosphate] since it was emerging as a possible new second messenger to mediate hormone effects," he writes in Les Prix Nobel, a publication of the Nobel Foundation.4
"Second messengers" are molecules that are involved in carrying a message from the outside of the cell to the inside. For example, when adrenaline circulates in the blood, it binds to the outside surface of cells in the vessels and the heart. When it binds to the cell surface, it triggers the production of a second messenger just below the surface of the cell. The second messenger then spreads throughout the cell to pass on the message. Cyclic AMP (adenosine monophosphate) is the "second messenger" for adrenaline; it passes on the message of adrenaline to activate the fight-or-flight response.
In his work with cyclic GMP, Dr. Murad found that it was, in fact, the "second messenger" for NO. When NO enters a cell, it activates an enzyme called guanylate cyclase, which produces the second messenger, cyclic GMP. In this way, cyclic GMP does the work of NO; it relaxes muscle cells. In effect, Dr. Murad had solved the mystery of how nitroglycerin causes blood vessels to relax. He had found that nitroglycerin released NO, which increased the activity of an enzyme (guanylate cyclase) that caused a chain reaction, resulting in relaxed muscle tissue.
This was a startling new finding because up until that time NO was mainly thought of as a product of car exhaust, a toxic gas that existed only outside the body. It was considered a poison and, to some, a nuisance. (Years later, Dr. Murad's discovery would have an impact on a new drug called Viagra. Viagra improves erections by increasing blood flow to the penis; it does this by preventing the breakdown of cyclic GMP. By extending the action of cyclic GMP, Viagra assists the action of nitric oxide, thus improving blood flow to the penis.)
From the Hardcover edition.