Do you see spots if you stand up too fast? Feel a tingling in your extremities? Break out in a cold sweat, or even faint? You may be suffering from lazy blood-vessel response.

“Moving from a seated to a standing position causes blood to pool in the legs,” notes Lawrence Sinoway, professor of medicine at Penn State Milton S. Hershey Medical Center. “In most people, the body compensates for the resulting drop in blood pressure by telling the blood vessels to narrow and rev up the pressure. When they don't constrict, blood pressure stays low, and temporarily the brain doesn't receive enough oxygen.”

That's when the room starts to go dark.

It's unclear exactly why, Sinoway says, but this form of dizziness most often afflicts older people. It may also occur in people with high blood pressure, or those who are dehydrated—and in anyone who's spent a few days lying in bed.

When a person stands, the brain sends a signal to the nerves that supply blood vessels in the leg muscles, which then release the hormone norepinephrine at the neurovascular junction within the muscle tissue—the spot where the nerves and vessels communicate. Although the precise mechanism is unclear, norepinephrine prompts vasoconstriction, boosting blood flow to the upper body until pressure regulates.

That's the theory. But, Sinoway says, “We actually know little about the role of norepinephrine in this regulation because our methods of measurement are so inadequate.” Typically, he explains, norepinephrine levels are measured by taking blood samples. “That gives a measure of what's in the blood stream. But what you really need to know is what's sitting in the muscle tissue just next to the blood vessel. That's the norepinephrine that plays a role.”

To get a more accurate measurement, Sinoway's team adapted a lower-body negative-pressure device—a sealed chamber the size of a small refrigerator, sometimes used to test circulatory responses to microgravity in astronauts—to simulate the pressure change caused by moving from a seated to a standing position. They used microdialysis probes—fine fibers passed through thin needles—to measure the amount of norepinephrine at the neurovascular junctions in the leg muscles of seven female and five male subjects. Micro-dialysis, Sinoway explains, measures fluid composition in the spaces between nerve, blood vessel, and muscle cells known as the interstitium.

Study participants laid flat on a padded table. After four to six probes were inserted into each leg, one leg was placed in the negative-pressure chamber. Once baseline measurements were attained, suction was applied to the chambered leg to mimic standing. In addition to measuring the chemical reactions to nerve signals, Sinoway used microneurography—a small needle inserted into a nerve in the leg to measure signals from the brain directly. Then he compared the norepinephrine levels measured by microdialysis to those found in blood samples taken from the same patients.

Simulated standing caused increased nerve activity, and boosted the amount of norepinephrine both in the blood plasma and in the interstitium, he reports. But, “The important finding is that the rate of rise of norepinephrine in the blood plasma was much less than the rate of increase found in the interstitium.”

Sinoway estimates that only one-fifth of the norepinephrine released by the muscle tissue actually reaches the blood stream. Even that small amount, he notes, is quickly metabolized, or broken down. Checking the amount of hormone in the blood stream, therefore, provides a very poor measure of its presence in the surrounding tissue where it does its work.

A more accurate measure, at the neurovascular junction, should help determine once and for all whether insufficient norepinephrine causes the blood-vessel “laziness” that leads to dizziness, Sinoway suggests.

But even if a lack of the hormone is found many questions will remain. “As is true of all human systems, there are great redundancies built into the vasoconstrictor system. Knocking out one mechanism for vessel narrowing may not be enough to cause fainting. For some people, too, insufficient norepinephrine may become a factor only when they are dehydrated, or have an infection, or begin taking certain heart medications or develop heart disease.”

To Sinoway's team, then, this study represents a start, not a finish. “However, it is an important new approach to the study of an area where we have surprisingly few answers.”

Lawrence I. Sinoway, M.D., is professor of medicine in the division of cardiology at the Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, 717-531-6853; lsinoway@psu.edu. Sinoway is also the program director of the General Clinical Research Center at Penn State Milton S. Hershey Medical Center, where the research reported above was conducted. One of 76 National Institutes of Health-sponsored centers of its type, the GCRC provides a centralized place for physicians to meet with patients who take part in clinical investigations. This study was published in the July 26, 2002, online edition of American Journal of Physiology: Heart and Circulatory Physiology.