As the body’s chief source of nitric oxide,
this amino acid combats endothelial dysfunction
By Will Block
ere’s a Ripley’s “Believe It or Not” for you: there are about 60,000 miles of blood vessels in the human body—enough to encircle the Earth 2.4 times. Think about that! (Or not, in case you’re afraid your head might explode.) Let’s see if Ripley was right. We’ll use nice round numbers to make it easy.
First of all, 60,000 miles is roughly 100,000 kilometers (km), or 100 million meters (m), or 100 billion millimeters (mm), or 100 trillion micrometers (µm). It’s estimated that there are about 40 billion capillaries in the circulatory system, and they constitute virtually all of it. So we can divide 100 billion mm by 40 billion capillaries, giving 2.5 mm (1/10 inch) per capillary. Since the diameter of a typical human cell is about 10 µm (but it varies widely), we can see that the length of a capillary, in this scenario, is equivalent to about 250 typical cells laid end-to-end.
Speaking of which, there are perhaps 10 trillion cells in the human body (including the capillary cells themselves, of course). If all of them were laid end-to-end, they too would encircle the Earth about 2.4 times, because 10 trillion x 10 µm = 100 trillion µm, which, as we saw above, is 100,000 km. (Many people would like to be tall and thin, but this is ridiculous!)
Hey, wait a minute—if the blood vessels alone are 100,000 km long, how could all the body’s cells add up to that same length? They couldn’t, of course—it would have to be a much greater length. The paradox stems from the fact that many of these figures are very rough indeed, especially the number of cells in the body, for which some estimates run as high as 100 trillion (24 times around the Earth).
Capillaries—Tiny, Delicate Workhorses
Capillaries are arguably the most important part of the circulatory system, because they accomplish the work—cellular nourishment—for which the system was designed in the first place. Arteries and veins are vital, to be sure, but they’re an infinitesimal part of the system in terms of its overall mileage. Nonetheless, they normally contain 95% of the blood (20% in the arteries and 75% in the veins), leaving only 5% in the capillaries.
As the thick-walled arteries that carry blood from the heart keep branching, they become ever narrower, and their walls become thinner and less muscular. Tiny arteries, still containing a thin layer of muscle cells, are called arterioles, and their continued branching results in the capillaries, whose gossamer-thin walls have no muscle cells. All that’s left is the one layer of thin, smooth, endothelial cells (held together by a wispy membrane) that form the inner lining of the entire circulatory system.
On the downstream side of the “capillary bed,” as the network is called, the merging vessels form tiny venules (the counterparts of arterioles). These venules merge to form veins, which carry blood back to the heart, where the cycle begins anew.
Cellular Nourishment by Diffusion and Transport
Healthy capillaries do a great job of nourishing all our cells (however many there may be), whose demand for blood-borne oxygen, glucose, fatty acids, lipids, hormones, amino acids, etc., never ceases. One of the 20 amino acids our cells need, by the way, is arginine, which, as we’ll see below, plays a key role in the function of the blood vessels that deliver it.
The diameter of a typical capillary is about 7–10 µm, and that of our flexible, disk-shaped red blood cells is 7.5 µm. Thus the red blood cells can squeeze through the capillary’s lumen (the channel) only in single file, and then often only by folding themselves into a bullet shape.* As they do so, their hemoglobin molecules (about 270 million of them per red blood cell) release their payload of oxygen molecules, which join other nutrients in nourishing our cells.
But the capillary and any given cell it nourishes are always a few micrometers apart—a vast distance by molecular standards—so how does the cell get the nutrients? By diffusion and transport. The blood-borne nutrients diffuse through the capillary wall (which is permeable to some kinds of molecules but not to others) into the extracellular fluid that bathes all of our cells. The nutrients then diffuse through the fluid to the cell wall, which can be breached in one of two ways. Some molecules diffuse through the wall, whereas others are “grabbed” (via intermolecular forces) by designated transporter molecules and are ferried through the wall (a complex process).
At the same time that all this is happening, cellular waste products, such as carbon dioxide and urea, either diffuse out or are transported out of the cell into the extracellular fluid; they then diffuse over to the capillary and through the capillary wall, to be whisked away by the blood and disposed of via the lungs or kidneys.
Atoms and Molecules Don’t Know Anything
These diffusion and transport processes, which seem almost magical in their exquisite coordination and apparent purposefulness, are well understood by physical chemists. They’re governed by the laws of chemical thermodynamics, which explain with mathematical precision how the atoms and molecules that participate in this tiny nutrition-and-waste-disposal drama “know” what to do, and when and where to do it, and how to do it.
The answer, of course, is that they don’t “know” anything at all—they’re just inanimate objects that obey the laws of chemistry and physics, which govern every detail of every interaction of every atom and molecule, at all times. What’s fabulous is that the sum total of all these interactions, and countless others throughout the body, is . . . life. It boggles the mind, even of those who understand it at a very deep scientific level.*
We Know a Lot—But Not Everything
Of course, not all aspects of physiology are well understood, even though all are governed by the same laws. One example: the mechanisms by which the cells of our blood vessels—particularly the all-important endothelial cells—regulate circulatory function. At every moment, they need to optimize the blood vessels’ ability to serve the ever-changing demands of the many different kinds of cells that constitute the various organs and tissues of the body. What a challenge!
Many different compounds of different kinds are involved in these molecular mechanisms, all of which interact with one another through positive and negative feedback loops so complex and subtle as to make one’s head spin. To further complicate matters, the function of the cardiovascular system is intimately intertwined with those of other bodily systems, most notably the kidneys and the adrenal glands.
Nitric Oxide—Arginine’s Potent Spawn
The scene of most of the blood vessels’ self-regulatory actions is the vascular endothelium, the layer of endothelial cells mentioned above. For example, it tells the muscles of the arterial walls when and how much to contract or expand, in different parts of the body, to meet ever-shifting needs for oxygen and glucose, our principal fuels. The muscle cells get the word via endothelial messenger molecules, of which the most important is nitric oxide (NO), a product of the metabolism of arginine.
NO is among the smallest and simplest of all biologically active molecules. What it lacks in size and complexity, it more than makes up for in chemical potency and versatility, in part because it’s a reactive free radical. In the circulatory system, NO is involved in vasodilation (the dilation of arteries and arterioles to reduce blood pressure and increase blood flow), the inhibition of platelet aggregation (blood clotting), various immune system defense mechanisms, and intracellular signaling. As a neurotransmitter, it acts in the brain, spinal cord, adrenal glands, and the nerves supplying the genitals.
Arginine Helps Reverse Anemia
There are different types of anemia, with different causes. One type is anemia associated with kidney failure. The specific cause of the disease is believed to be damage to certain cells associated with the capillaries that supply the renal tubules, which are part of the kidneys’ waste-filtration and disposal system. These cells secrete erythropoietin, a protein that stimulates the production of erythrocytes, or red blood cells. Even mild kidney failure can reduce the blood levels of erythropoietin.
© iStockphoto.com/Aaliya Landholt
Patients with chronic kidney failure have low levels of arginine, which plays a vital role in kidney function, mainly through its production of nitric oxide.* Researchers in Japan recently conducted a study to see whether supplemental arginine would increase hemoglobin levels in anemic patients with kidney failure that was chronic, but not so severe as to require dialysis. In this small, nonrandomized, non-placebo-controlled trial, they gave 1.3 g of arginine daily for 12 to 22 weeks to eight elderly patients (average age 83).
By the end of the study, five of the eight patients had experienced moderate increases in erythropoietin levels, and all eight experienced increases in hemoglobin levels; discontinuation of the arginine treatment caused hemoglobin levels to decline again. This led the authors to suggest that arginine was effective in treating anemia associated with kidney disease.
- Tarumoto T, Imagawa S, Kobayashi M, Hirayama A, Ozawa K, Nagasawa T. L-Arginine administration reverses anemia associated with renal disease. Int J Hematol 2007;86:126-9.
Inadequate Arginine Can Lead to ED
A characteristic feature of several chronic diseases—notably hypertension, hypercholesterolemia, atherosclerosis, and type 2 diabetes—is endothelial dysfunction, or ED. This is a different and far more dangerous kind of ED than that other one, the one we hear about ad nauseam on TV; the irony is that this ED causes that ED. It’s a failure of the vascular endothelium to perform well in its appointed tasks, one of which is to facilitate erections. ED is a predictor of heart attack and stroke, which are the number 1 and number 3 causes of death, respectively, in the USA.
Obesity is a major contributing factor in this disorder, and smoking has ED (both kinds) written all over it. The dysfunction itself is caused largely by inadequate NO levels, which can be brought about by many different factors, one of which is inadequate circulating or intracellular levels of arginine. A recent review article on the role of arginine in cardiovascular disease emphasizes the important role of various molecular mechanisms by which arginine molecules are transported into our cells. This complicated process plays a key role in the bioavailability of arginine and hence its ability to produce NO where and when it’s needed.
Ladies and Gentlemen, Place Your Bets
The details of the study are too technical to describe here, so let’s just hear the authors’ conclusion:
Optimal endothelial function is an integral component in maintaining vascular health. As such, NO is a critical participant in this process, and by extension, the bioavailability of NO and the factors that determine it are key physiological and pathophysiological processes. Endothelial dysfunction is a common phenotype seen in numerous cardiovascular diseases, such as coronary artery disease, stroke, and heart failure, and it is possible that limitation of substrate (L-arginine) availability for NO biosynthesis might play a pivotal role in the development of endothelial dysfunction seen in these cardiovascular disease states.
In other words, it’s important to maintain optimal circulating levels of arginine, if we want to cover our bets where our cardiovascular health is concerned.* And speaking of bets, you might win a few on the question of how long the circulatory system really is. If your victims tend to doubt your veracity (gasp!), just show them this copy of Life Enhancement—and suggest that they read it cover to cover!
- Chin-Dusting JPF, Willems L, Kaye DM. L-Arginine transporters in cardiovascular disease: a novel therapeutic target. Pharmacol Therapeut 2007;116:
Will Block is the publisher and editorial director of Life Enhancement magazine.