doctor talking to patient (448 x 299)

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, there is one reason you would not want to be like this gentleman. He is a prime candidate for erectile dysfunction.

The ability to achieve and maintain an erection is fundamentally a vascular event. The firmness is produced by opening the inflow of blood into the penis and shutting down or reducing the blood that is leaving that organ. Of course, the inflow of blood depends on the condition of the arterial supply to the penis and so, 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.

Nitric oxide is produced in the endothelium, a thin sheet of cells that lines every artery in the body. The entire mass of endothelium is a very large organ that produces a number of substances that affect the structure and function of the artery. Nitric oxide is a powerful artery dilator and 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. Nitric oxide is anti-inflammatory, anti-proliferative (interfering with thickening and narrowing ), anti-coagulant, and vasodilating. In short, nitric oxide does almost everything that you would like to see done in promoting arterial health. Very interestingly, all risk factors for arterial disease are associated with diminished endothelial function and thereby decreased nitric oxide production—and erectile dysfunction.

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 hypertension, high cholesterol, high triglycerides, metabolic syndrome, diabetes, and cigarette smoking. In fact, spending 30 minutes in a smoky bar can produce a measurable decline in arterial dilation. When endothelial dysfunction becomes sufficiently advanced, erectile dysfunction occurs. Erectile dysfunction is a very good early indicator of endothelial dysfunction. The endothelium, and nitric oxide production, play such a central role in the cardio-metabolic underpinnings of vascular disease that many physicians who are specialists in this area consider themselves endotheliologists. They select their medical therapies specifically to enhance nitric oxide production and improve the endothelial function in the patient with arterial disease or vascular risk factors.

Now things start to get really interesting. When the development of Viagra started, the researchers involved were looking for a way to increase nitric oxide levels in the artery and to improve arterial structure and function. 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. The researchers found that Viagra did not have much benefit as a cardiac drug—and then they noticed that amazing side effect and the rest is history. This is a case where serendipity produced a blockbuster drug.

Viagra improves nitric oxide levels very quickly, but there are other medications used in the medical treatment of arterial disease that have that same effect. ACE inhibitors, angiotensin-receptor blockers (ARBs), and amlodipine are important medications in the treatment of hypertension and they rapidly improve nitric oxide activity. 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 work specifically by reducing the effect of angiotensin II. Losartan, an angiotensin receptor blocker, 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 very rapidly and there are reports of improved erectile function related to these medications. The TZD drugs for diabetes increase nitric oxide levels. Some medications used for high blood pressure may cause problems with sexual activity, but the best drugs improve arterial structure and function, reduce the incidence of stroke, heart attack, and diabetes, and may—over time—improve erectile function.

High blood pressure is not a disease. It is a measurement. The elevation of the blood pressure tells us that the artery is abnormal in structure and function. Erectile dysfunction is like an early warning system. It tells us that the arterial system has enough disease that it does not work properly. If you have that problem, you may want to see a medical specialist rather than a urologist for a vascular evaluation. You want to see someone who is very well-versed in the medical management of vascular disease. And, while you are at it, you just might want to buy yourself a cowboy hat and a sheepskin jacket.


  1. Viagra and its cousins don’t work to enhance NO production, but further down the same pathway. The primary ‘second messenger’ for NO in target cells is cyclic GMP, produced when NO binds to activates the soluble guanylate cyclase enzyme. These drugs extend the lifetime of cGMP by inhibiting other enzymes that break it down. This increases the effect of the existing NO levels. The effect is similar since it’s downstream in the same signaling pathway.

  2. I’m impressed by the way you transposed the commercial into medical erectile problems. I guess the Marlboro people never thought that might happen.

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