Public Release: 

Study adds to knowledge of what it takes to stand up, walk

Penn State researchers measure norepinephrine release, vasoconstriction under lower body pressure

Penn State

Standing up too quickly can cause some people - especially the elderly - to become dizzy and even faint.

What's often to blame? Lazy blood vessel response.

A study by Penn State College of Medicine researchers provides new data on blood vessel function and reveals the benefits of a measurement technique that gives more accurate data on the amount of norepinephrine (n r' ep-e-nef' rin) - a hormone vital for blood vessel response - in tissues adjacent to blood vessels. The study, led by Lawrence Sinoway, M.D., program director of the General Clinical Research Center (GCRC) at Penn State Milton S. Hershey Medical Center, and professor of medicine, Division of Cardiology, Penn State College of Medicine, was published July 26, 2002, in the online edition of American Journal of Physiology: Heart and Circulatory Physiology. Moving from a seated to standing position causes blood to pool in the legs. In most people, the body compensates for this drop in blood pressure by releasing norepinephrine, which triggers vasoconstriction, or blood vessel narrowing. Vasoconstriction revs up the pressure in the vessels and maintains adequate blood pressure. When a person stands and the vessels don't constrict, blood pressure drops and, temporarily, the brain doesn't receive enough oxygen. This causes dizziness and fainting.

Typically, norepinephrine levels are measured by taking blood samples.

"But because the norepinephrine sits in the tissue as well as in the blood plasma, when you measure it only in blood, you only account for a small part of it," Sinoway said. "What you really need to know is what's sitting in the muscle right next to the blood vessel because it's that norepinephrine that will signal vasoconstriction and maintain blood pressure when you stand up."

Conducted at the National Institutes of Health-funded GCRC, Sinoway used microdialysis to measure the muscle sympathetic nerve activity - or muscle activity prompted by signals from the Central Nervous System (CNS) - in 7 men and 5 women. All provided informed consent approved by the Institutional Review Board of the Penn State Hershey Medical Center.

Microdialysis uses tiny probes to measure fluid composition in interstitial tissue - spaces outside of cells - and the changes in that fluid when exposed to certain factors. In this study, microdialysis was used to measure norepinephrine near the blood vessels in leg muscle both at rest and when the lower body is under pressure. The pressure applied to the lower body mimics the action of someone moving from a seated to standing position.

In addition to microdialysis to measure the chemical reactions to CNS signals, Sinoway also used microneurography to record the intensity of the "messages" sent by the CNS and directed to blood vessels. Blood samples also were taken to compare the norepinephrine levels.

Subjects were placed on a padded table with the left leg and pelvis placed in a lower body negative pressure (LBNP) chamber specifically designed and built for this study. The right leg was left outside of the chamber so that microdialysis and microneurography could be performed. An I.V. was inserted in the arm. Patients' heart rates were continuously monitored.

After baseline microdialysis measurements and blood samples were taken, the pressure was slowly increased in the chamber and additional readings and blood samples were recorded.

"One-legged LBNP led to a rise in muscle sympathetic nerve activity, the amount of norepinephrine in the blood plasma, and the norepinephrine in the interstitium, or tissue near the blood vessels," Sinoway said. "The important factor is that the rate of rise of norepinephrine in the blood plasma was much less than the rate of increase found in interstitial norepinephrine."

The reason: Blood samples give only the amount of norepinephrine that reaches the blood stream. Such samples don't take into account the norepinephrine near blood vessels where the hormone plays its crucial role in causing vasoconstriction.

"In a broader sense, this study adds to our knowledge of how the blood vessels work and how we're able to stand up and walk," Sinoway said.

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This work was supported by a Dean's Feasibility Grant from Penn State University, a Veterans Administration Merit Review Award, National Aeronautics and Space Administration grants, National Institutes of Health grants and the NIH-funded General Clinical Research Center at Penn State Milton S. Hershey Medical Center.

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