Do you remember the guy on the cigarette commercial—the ruggedly handsome, cool cowboy with the hat and the sheepskin jacket? The message was clear—smoke a cigarette and you can be like me! Well, guys, there is one reason you would not want to be like this gentleman. He is a prime candidate for erectile dysfunction because of the detrimental effect of cigarettes on the health of his arteries. The ability to achieve and maintain an erection is fundamentally an arterial event. Firmness of the penis is produced when the blood flowing into the penis gets trapped by the expansion of the sinusoids in the corpora cavernosa. Of course, the inflow of blood to the penis depends on the condition of its arterial supply. And, it is important to understand that the health of the penile arteries often reflects the health of the arteries in the body in general. Therefore, erectile dysfunction becomes an early warning signal for arterial disease. This is a great topic to help understand the central role of nitric oxide in the arterial system. The role of nitric oxide in erectile dysfunction Nitric oxide (NO) causes arteries to dilate or expand. This leads to an increase in blood flow through those blood vessels. Viagra, and drugs like it, cause nitric oxide to accumulate which, in turn, dilates the penile arteries. This provides more blood flow to the penis and an improved erectile function. Nitric oxide is produced in the endothelium, the thin sheet of cells that lines every artery in the body. The entire mass of endothelium is, in fact, a very large organ that produces a number of substances that affect the structure and function of the artery. When the endothelium has been damaged by too many oxidative particles or other types of insults, it leads to a decrease in endothelial function and reduced NO production. One of the first signs of decreased endothelial function is the inability to achieve a satisfactory erection. This is because the penile arteries cannot dilate sufficiently. This is not just an inconvenience. Remember, endothelial dysfunction also affects the heart arteries. With exercise, the heart arteries ordinarily dilate, but in the patient with endothelial damage, they may contract instead. This is really bad for patients with heart disease. It may contribute to inadequate blood flow to the hears which can cause chest pain. Nitric oxide is a powerful artery dilator Nitric oxide is a powerful artery dilator. It is produced in every artery in the body—from your hair roots to your toenails. It is the active ingredient in nitroglycerine. When you place a nitroglycerine tablet under your tongue, the nitric oxide level in the bloodstream is increased and all arteries dilate. It increases the blood flow to the heart and that relieves chest pain. Nitric oxide is anti-inflammatory anti-proliferative (interfering with thickening and narrowing) anticoagulant vasodilating In short, nitric oxide does almost everything that you would like to see done to promote arterial health. Interestingly, all risk factors for arterial disease are associated with diminished endothelial function and thereby decreased nitric oxide production—and erectile dysfunction. ADMA – the uber marker In many ways, the factors that lead to erectile problems represent a vicious cycle. Nearly all vascular risk factors are associated with increased levels of a molecule named asymmetric dimethylarginine (ADMA). Leading scientists at Stanford even wrote an article describing ADMA as an “uber marker.” This is because it is a common denominator linking all risk factors for vascular disease. Indeed, ADMA is increased in the following conditions: insulin resistance high cholesterol high triglycerides high blood pressure diabetes chronic kidney disease aging It may even increase acutely. For example, ADMA increases enough after drinking a milkshake to impair endothelial function 30 minutes later. ADMA directly decreases nitric oxide availability by blocking nitric oxide production by endothelial nitric oxide synthase (eNOS). It also changes eNOS function directly to produce more oxidative particles. These reactive oxygen species or ROS in turn further damage the endothelium. Endothelial dysfunction occurs early in atherosclerosis Endothelial dysfunction occurs very early in vascular disease. It precedes the development of high blood pressure. It occurs in the very earliest stages of atherosclerosis. The first stage of atherosclerotic disease of the artery is the fatty streak. Young soldiers who were killed in action in Korea and Vietnam were found to have fatty streaks in the artery. These were men in their late teens and twenties. These youngsters with fatty streaks had diminished nitric oxide activity. Nitric oxide production is predictably reduced in patients with the following conditions: hypertension high cholesterol high triglycerides metabolic syndrome diabetes cigarette smoking. In fact, spending 30 minutes in a smoky bar can produce a measurable decline in arterial dilation. A single puff of cigarette smoke contains 1015 oxidative particles. When endothelial dysfunction becomes sufficiently advanced, erectile dysfunction occurs. Viagra slows the breakdown of nitric oxide When the development of Viagra started, the researchers involved were looking for a way to increase nitric oxide levels in the artery. They hoped that by doing this, they would be able to improve arterial structure and function. But, nitric oxide is like a faint mist in a wind storm. It is degraded in seconds. Viagra works by slowing the breakdown of nitric oxide and causing it to accumulate in the circulation. Researchers, however, found that Viagra did not offer much benefit as a cardiac drug. But they did notice an amazing side effect. It increased blood flow to the penis and helped men attain and maintain an erection. The rest is history. This is a case where serendipity produced a blockbuster drug. Other medications impact nitric oxide levels as well Viagra improves nitric oxide levels very quickly. However, there are other medications used in the medical treatment of arterial disease that have that same effect. These include: ACE inhibitors angiotensin-receptor blockers (ARBs) amlodipine metformin statins They are all important medications in the treatment of vascular risk factors and they all improve nitric oxide activity. Angiotensin II is a bad actor in the artery Nitric oxide and angiotensin II are a kind of yin-yang in vascular disease. When angiotensin II activity is high, nitric oxide activity is reduced and vice versa. Angiotensin II is a bad actor in the artery. ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin-receptor blockers) work specifically by reducing the effect of angiotensin II. Losartan, an ARB, has been proven over the course of a year to improve arterial function (dilation related to nitric oxide) and structure (reduction of the abnormal thickness of the artery). Not surprisingly, there are reports in the medical literature that treatment with Losartan improves erectile function. Statin drugs for cholesterol and metformin for diabetes also improve endothelial function rapidly. Metformin directly blocks ADMA to increase NO and reduce oxidative particle production. There are also reports of improved erectile function related to these medications. Some medications used for high blood pressure may cause problems with sexual activity. However, the best drugs improve arterial structure and function, reduce the incidence of stroke, heart attack, and diabetes, and may—over time—improve erectile function. The bottom line erectile dysfunction is like an early warning system for arterial health. When it occurs, it tells us that the arterial system has enough disease that it is no longer working properly. Source
