Monday, December 15, 2003

Nitrate Linked To Artery Health
By Mike Upchurch

A naturally occurring byproduct of nitric oxide production in the body may play a major role in diagnosing blood vessel health. Nitrate, according to a Duke study presented at the scientific sessions of the Society for Free Radical Biology and Medicine, may represent an easy method of assessing the health of stressed arteries.

Jason Allen, PhD

“This is the first study to attempt to link whole body production of nitric oxide with regional endothelial function," said Jason Allen, PhD, who presented the results of the study. "Both measures were found to discriminate between healthy participants and those with diagnosed cardiovascular disease."

Endothelium is the tissue that lines the walls of arteries. In addition to dilating blood vessels, nitric oxide production is a key factor in an artery’s ability to constrict and relax in response to the body’s demands for blood. In patients with cardiovascular disease, arteries are frequently unable to rebound back to normal after periods of stress or injury due to damaged endothelium.

Dr. Allen and his colleagues enrolled 37 patients in their pilot study and randomized them to 1 of 3 groups: healthy patients; those with 2 or more known risk factors, such as diabetes or high blood pressure, but no diagnosed cardiovascular disease; and those patients with known disease.

The investigators used ultrasound to measure the response of the patient’s brachial arteries, the main artery in the arm, to stress. They assessed the artery at baseline, while it was being closed by a tourniquet, and after the tourniquet was released.

"When the tourniquet is loosened, the resulting increased blood flow causes physical shear stress to the endothelium," Allen explained. "A healthy artery should be able to react to the increased blood by dilating. Conversely, an unhealthy or diseased artery will not be able to respond as well. This response of the endothelium is regulated in part by nitric oxide."

While the diameters of arteries in all 3 groups increased, the healthy group saw the largest increase after 60 seconds, possibly indicating greater endothelial health and nitric oxide production.

Blood samples were then taken from the patients as they rested, immediately after heavy exercise, and again 10 minutes later.

Only the healthy patients had in increase in their nitric oxide levels while they were recovering from the exercise. The healthy patients’ brachial arteries also responded better to the stress of increased blood flow.

Using nitrate assessment as a diagnostic tool could be significant, Allen explained, because nearly half of all patients who develop heart disease do not have the usual risk factors such as diabetes or smoking. A simple, noninvasive measure of their nitric oxide production could help doctors paint a more accurate picture of their risk level.

Dr. Allen and his team suspected that exercise may help the higher-risk patients achieve similar outcomes as the healthy subjects in their study. Six of the at-risk patients underwent 6 months of regular exercise on treadmills or similar equipment. After the exercise program, the research team once more took blood samples and performed ultrasound assessments.

The patients showed significant increases in nitrate levels, indicating greater nitric oxide production. Their brachial arteries ability to dilate also nearly doubled, suggesting better protected endothelium.