Stress test has less effect on blood vessels when hormone cortisol is blocked

Negative effects of the hormone cortisol on the inner lining of blood vessels, the endothelium, may explain how stressful events trigger heart attacks and other cardiovascular problems, according to a new study in the July 19, 2005, issue of the Journal of the American College of Cardiology.

“It is already known that acute stress impairs endothelial function. Our study suggests that cortisol may cause this,” said Michael P. Frenneaux, F.R.C.P., F.A.C.C., of the University of Birmingham, United Kingdom.

The researchers, including lead authors Andrew J. M. Broadley, M.R.C.P., and Ania Korszun, M.R.C.Psych, gave mental stress tests to 36 healthy nonsmokers. Before the stress tests, the participants were randomly assigned to receive a drug, metyrapone, which blocks the action of cortisol, or a placebo pill. The randomization was double-blinded; meaning neither the researchers nor the participants knew who was given the active drug until after the study was completed. Blood pressure patterns (baroreflex sensitivity) and a measure of how the endothelial layer of blood vessels in the arm responded to sudden changes in blood flow (flow-mediated dilation) were recorded before and after the mental stress tests.

Both measures fell in the placebo group, which indicated the stress was impairing the responsiveness of the blood vessels. This sort of impaired response is one early warning sign of cardiovascular disease. By contrast, the measurements were unchanged in the participants who had been given the cortisol-blocking drug.

“Blocking cortisol synthesis with metyrapone prevented the impairment of endothelial function which follows acute mental stress in healthy subjects,” Dr. Frenneaux said.

This study was designed only to reveal the role of cortisol in the body’s response to stressful events. Dr. Frenneaux said they are not suggesting metyrapone as a potential antistress preventive treatment. He also pointed out that this study looked only at the short-term response to stress, not the effects of chronic stress.

He said that they cannot rule out the possibility that metyrapone may have had a direct effect on blood vessel responses to stress, in addition to blocking the action of cortisol. However, he noted that laboratory studies did not show any such direct effect of the drug.

Dr. Frenneaux said that because they studied healthy participants, their results may apply to a broad segment of the population, not just people with heart disease who are at high risk of cardiac events.

“Cortisol plays an important role in the impairment of endothelial and baroreflex function precipitated by acute stress,” he said.

Todd Anderson, M.D., F.R.C.P., at the University of Calgary, Alberta, Canada, who was not connected with this study, said it helps explain how stressful events trigger heart attacks and other cardiac events.

“It is well known that stress may play a role in cardiovascular disease but mechanisms have remained unclear. Changes in blood pressure, lipids and plaque rupture are but a few of those proposed,” Dr. Anderson said. “The current study helps explain some of the possible mechanisms of stress-induced increases in cardiovascular risk. Further studies are required to see if this is important long term and if there are any therapeutic options for dealing with this phenomenon.”