CLAMP DOWN

Snorting coke narrows arteries, with potentially deadly results

COCAlNE-induced heart attacks are the result of severe constriction of the
arteries, not just excessive oxygen demand as was previously thought. The
same mechanism may also explain how heart attacks can be caused by stress
and depression, and sheds light on why women are less prone to such attacks,
say researchers in Germany.

People who snort cocaine can suffer heart attacks days after using the drug.
About a third of those who suffer cardiac arrest have no evidence of heart
disease.such as plaque build-up in their arteries. Even newborn babies whose
mothers used the drug while they were pregnant have been known to have heart
attacks. But doctors have been unable to explain why.

Now Rainer Arendt and his colleagues at the University of Munich think they
might have part of the answer. They took from pigs the endothelial cells
that line heart vessels, cultured them and exposed them to cocaine. Then
they measured the hourly release rates of endothelin, the body's most potent
vasoconstrictor.

They found that as they stepped up the cocaine, the levels of endothelin
increased dramatically. This suggests cocaineinduced heart attacks occur
when the blood vessels constrict so rnuch that they cut off the heart's
blood supply, Arendt says.

Cocaine stimulates endothelin release by binding to so-called sigma
receptors in the vessel lining. When the researchers applied the drug
haloperidol, which blocks the sigma receptor, endothelin release stopped.
The female hormone progesterone is also known to block the sigma receptor,
opening up the field to exploring gender differences in heart disease, says
Arendt.

The researchers decided to find out if cocaine abusers really do have
heightened levels of endothelin, as the cell culture experiments suggested.
They took urine and blood samples from 12 people high on cocaine and
compared them to samples from 13 nonusers. The concentration of endothelin
in the addicts' urine and blood was almost four times higher than it was in
the control group (Circulation, vol 98, p 385).

Arendt thinks the same mechanism may underlie heart attacks associated with
stress and depression, which have previously puzzled doctors. He says
cocaine activates many of the same pathways as stress.

Arendt suspects that there is an unidentified natural trigger that binds to
sigma receptors in the same way as cocaine and stimulates endothelin
release. "Sigma receptors provide a missing link to explain the influences
of depression, mood and mental stress on coronary reactivity," says Arendt.

Checked-by: Don Beck