Birmingham, UK - A new study suggests that the hormone cortisol may be responsible for the endothelial dysfunction that occurs as a result of acute stress .
The study, published in the July 19, 2005 issue of the Journal of the American College of Cardiology, found that blocking cortisol inhibited endothelial function associated with stress.
Senior author Dr Michael Frenneaux (University of Birmingham, UK) told heart wire that other research conducted by his team suggested that cortisol is also involved in the association between depression and heart disease. "Our studies emphasize the link between mind and body and open up opportunities to try to prevent heart disease caused by stress and depression," he commented.
In the paper, the researchers, including lead authors Drs Andrew Broadley (Torbay Hospital, Torquay, UK) and Ania Korszun (Bart's and the London Queen Mary College of Medicine and Dentistry, London, UK), explain that mental stress is known to cause endothelial dysfunction and impaired baroreflex sensitivity and to be associated with increased coronary heart disease morbidity and mortality, especially from sudden cardiac death.
Given that cortisol is a key component of the stress response and administration of cortisol has been shown to impair endothelial function in healthy people, they designed a study to investigate whether blocking cortisol production with metyrapone would prevent stress-induced endothelial dysfunction.
They measured endothelial function and baroreflex sensitivity in 36 healthy volunteers without CHD risk factors who were then randomized to receive oral metyrapone or placebo. Five hours later the volunteers were subjected to mental stress (a simulated public-speaking task previously shown to produce endothelial dysfunction in the brachial artery), and then endothelial function and baroreflex sensitivity were remeasured.
Both measures decreased in the placebo group, indicating endothelial dysfunction, but were unchanged in the participants who had been given metyrapone.Stress and depression both linked to heart disease
Frenneaux commented to heart wire : "We have shown that metyrapone blocks the endothelial dysfunction and the baroreflex response caused by stress. We have also shown in studies not yet published that patients with depression have endothelial dysfunction and that metyrapone also normalizes this. Therefore, cortisol appears to be an important mediator between stress and depression and vascular changes."
He added: "We know depression carries with it a long-term increased risk of vascular events. We also know that acute stress can trigger vascular events in the short term. Cortisol may be that link. Cortisol seems to be involved in both these processes." But Frenneaux explained that metyrapone is not suitable for use as a clinical drug to prevent these effects. "It is too powerfulit blocks the cortisol system entirelytoo much like a blunt instrument. We need to more subtly alter the cortisol system."A role for eplerenone?
He noted that other groups are looking at the mineralocorticoid antagonist eplerenone in this regard. It has been suggested that abnormal function of the mineralocorticoid receptors causes an increase in cortisol, and blockade of these receptors with eplerenone might therefore normalize cortisol levels. "They are focusing on the link between depression and heart disease and investigating whether eplerenone bocks that link, but it might also work in acute stress," Frenneaux said.
Commenting on the present research study in an American College of Cardiology press release, Dr Todd Anderson (University of Calgary, AB), who was not connected with this study, said: "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," 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 whether this is important long term and whether there are any therapeutic options for dealing with this phenomenon."
Heartwire from Medscape © 2005
Cite this: Cortisol may mediate stress-induced endothelial dysfunction - Medscape - Jul 21, 2005.