A bi-polar hormone that can contribute to strokes and minimize their damage is emerging as a therapeutic target in the battle against these brain attacks, researchers say.
"It costs about $56 billion a year to look after stroke patients, never mind the quality-of-life issues for these patients," says Dr. Anne M. Dorrance, Medical College of Georgia physiologist and senior author of a review article in Trends in Endocrinology and Metabolism.
Despite better management of blood pressure – the number-one risk factor for strokes – stroke incidence is not declining and aging baby boomers likely will cause rates to spike, says Dr. Dorrance.
She is among an increasing number of scientists who think the hormone, aldosterone, is part of the problem and blocking it may be part of the solution. Scientific momentum surrounding the hormone secreted by the adrenal gland prompted the journal to ask Dr. Dorrance to write the article, "Aldosterone: Good Guy or Bad Guy in Cerebrovascular Disease."
She calls aldosterone "a double-edged sword" that helps maintain healthy blood pressure but also dangerously reshapes blood vessels and makes the heart fibrotic. Its conflicting roles in the body are clearly played out in the brain of hypertensives.
"What aldosterone does under normal circumstances is regulate sodium balance in the body," says Dr. Dorrance. When sodium levels rise, aldosterone levels drop so the kidneys will eliminate more sodium to help maintain a healthy blood pressure and vice versa. "Ten years ago, we would have told you all aldosterone does is work on the kidneys," she says.
In recent years, Dr. Dorrance and others have learned aldosterone works in many ways – many of them bad – inside blood vessels throughout the body and brain where there are many aldosterone receptors.
As with most things, too much aldosterone – resulting from an adrenal gland tumor or abnormal production for unknown reasons – is what causes problems, such as proliferation of the smooth muscle cells that make up the elastic walls of blood vessels. Instead of the middle filling up with plaque as it does in atherosclerosis, the middle, or lumen, of the blood vessel shrinks because the walls thickens. To further set the stage for stroke, the thicker walls are less stretchy, Dr. Dorrance says.
Conversely, after a stroke, emerging evidence suggests aldosterone helps neurons survive. "This is still a very big 'perhaps,' but perhaps at the time of a stroke, it may be beneficial, but only within the brain," Dr. Dorrance says of high aldosterone levels. "There is a huge caveat because aldosterone does not get into the brain terribly well."
Other good news emerging is that adolesterone blockers, such as spironolactone and a newer, more specific blocker eplerenone, may help turn the tide. Spironolactone was developed as an antihypertensive years ago but didn't work very well, Dr. Dorrance says. Then, a University of Michigan study in the mid-1980s showed heart failure patients who got the drug in addition to standard treatment, such as beta blockers and ACE inhibitors, basically stopped dying, says Dr. Dorrance, who came from the University of Michigan to MCG as a postdoctoral fellow in 2000.
Unfortunately spironolactone also blocks testosterone so it increased men's breast size. Last year, a more-specific second generation of the drug, eplerenone, received Food and Drug Adminstration approval.
Still neither version has become a medicine cabinet mainstay. However the potential for aldosterone blockers may still be unfolding as researchers such as Dr. Dorrance discover what the hormone does and what blocking it prevents.