Aug. 7, 1998 DALLAS, Texas, Aug. 4, 1998 -- It's well documented that cocaine can over-stimulate the heart and cause a heart attack. In a new study, researchers say they may have found one reason why this happens, offering new hope for treatment.
In a study published in today's Circulation: Journal of the American Heart Association, German scientists say cocaine attacks cells in the endothelium, a layer of cells that lines the inside of blood vessels. Cocaine spurs the cells to release into the bloodstream large quantities of endothelin, a chemical which signals blood vessels to contract.
The researchers say that cocaine especially wreaks havoc with what are known as sigma receptors, which are located in the body's cells.
Sigma receptors instruct cells about how to react when changes occur in the body. Sigma receptors have primarily been found in the brain where they may play a role in regulating mood, according to the researchers.
In studies of pig cells, the scientists found that cocaine causes the sigma receptors in the cells lining blood vessels to go haywire by directing them to release a higher than normal amount of endothelin. Excessive amounts of the chemical can make blood vessels constrict faster and tighter, thereby choking off blood supply to the heart.
"The novel finding of sigma receptors in the endothelium may be a missing link in the brain-heart connection, explaining how the brain in depression or stress signals the coronary arteries to contract," says the study's senior author, Rainer Arendt, M.D., of the University of Munich, Germany. "This finding opens the opportunity to develop powerful drugs to fight against cocaine's effects.
"Not only will this provide a needed help in the occasionally difficult medical therapy of treating cocaine-induced heart attack or stroke, but it may prove to be important in understanding stress-related heart attacks and cardiac arrests. Cocaine seems to use the same pathways that are activated in the body's response to stress."
After identifying cocaine's effects on blood vessels, the researchers turned their attention to ways to block these effects.
By using two drugs that readily interact with sigma receptors, the scientists stopped the cocaine-induced release of endothelin from cells. Used in healthy cells unaffected by cocaine, the drugs haloperidol and ditolylguanidine did not show significant effects on reducing the release of endothelin. Using haloperidol alone eliminated all effects of cocaine on endothelin release.
Ditolylguandine also was shown to significantly reduce the increased release of endothelin that is associated with cocaine, but not completely eliminate the effects of cocaine.
Arendt and his colleagues examined blood and urine samples of 12 cocaine-intoxicated people and 13 healthy non-users. The endothelin levels in blood and urine were 3 to 3.5 times higher in people who had used cocaine when compared to the individuals who had not.
"The coincidence of cocaine intoxication in people with extremely high endothelin levels in blood and urine reported in our study is not formal proof, but stark evidence that cocaine does stimulate the endothelin release in humans as well," says Arendt.
Arendt stops short of saying that the sigma receptor phenomenon is the only explanation for cocaine-related cardiovascular disease.
"All of the cocaine-intoxicated patients in our study had elevated endothelin levels, but they did not all have a heart attack or stroke," he says. "That means other factors come into play. It is likely that the interaction between endothelin and other constricting chemicals causes prolonged constricting of the blood vessels in the heart and brain."
Co-authors are Ute Wilbert-Lampen, M.D.; Christian Seliger, M.S.; and Thomas Zilker, M.D.
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The above story is reprinted from materials provided by American Heart Association.
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