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Researchers find why prostate drug increases likelihood of heart failure

Doxazosin, a drug commonly prescribed to help improve urinary flow in men with enlarged prostates, increases the likelihood of heart failure by blocking specific receptors in heart muscle cells, according to a study conducted at the San Francisco VA Medical Center.

The cell receptors, named alpha 1-adrenergic receptors, increase the contraction of smooth muscles. Drugs such as doxazosin promote better urinary flow by blocking the action of these receptors, thus relaxing the muscles that control the flow of urine.

In the study, mice that lacked alpha 1 receptors were subjected to conditions mimicking high blood pressure. Half died of heart failure and the rest developed dilated cardiomyopathy, a severe form of heart disease. Both outcomes were apparently due to loss of alpha 1 signaling ability in heart muscle cells.

One hundred percent of normal mice survived when subjected to the same conditions. The study appears in the April, 2006 issue of Journal of Clinical Investigation.

"While you can't jump to conclusions about humans based on mouse results, it might not be a good idea to block this receptor," says principal investigator Paul C. Simpson, MD, a staff cardiologist at SFVAMC. "I think doctors and researchers need to pay more attention to the possibility that these drugs are making people worse."

The study authors note that in a large national prospective study called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, sponsored by the National Heart, Lung, and Blood institute and conducted from 1994 to 2002, a test of doxazosin was stopped early because subjects taking it proved to be at substantially increased risk for heart failure.

Nonetheless, according to Simpson, a very large number of men with prostate problems continue to take drugs known as alpha 1 blockers.

"This current study gives a probable mechanism for heart failure in those patients, and shows that alpha blo
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Contact: Steve Tokar
steve.tokar@ncire.org
415-221-4810 x5202
University of California - San Francisco
3-Apr-2006


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