Endothelium-dependent vasorelaxation is impaired in cocaine arteriopathy.
OBJECTIVE
This study sought to assess endothelium-dependent vasorelaxation in long-term users of cocaine.


BACKGROUND
Cocaine use has been associated with myocardial infarction, stroke and intestinal infarction. Previously demonstrated effects of the drug, including increased heart rate and blood pressure and increased vascular tone, do not explain the sporadic nature of these vascular events or the occurrence of ischemia remote from acute administration. Abnormal endothelial function could contribute to focal vasospasm and thrombosis and predispose to premature atherosclerosis, all of which have been demonstrated in cocaine users with myocardial infarction.


METHODS
Using plethysmography, we studied the change in forearm blood flow in response to intraarterial acetylcholine and nitroprusside in 10 long-term cocaine users and 13 control subjects of similar age who had not used cocaine; sample size was based on a 70% power to detect a 20% reduction in flow with acetylcholine between subjects and control subjects. Using graded doses of intracoronary acetylcholine (from 10(-9) to 10(-6) mol/liter), we studied a second group of 10 cocaine users with angiographically normal or near-normal arteries.


RESULTS
Mean forearm blood flow during acetylcholine infusion was significantly lower in cocaine users than in control subjects (p = 0.02). During nitroprusside infusion, there was no difference (p = 0.2) between cocaine users and control subjects. Cigarette smoking did not explain the differences between cocaine users and control subjects. Acetylcholine elicited coronary vasoconstriction in 8 of 10 subjects.


CONCLUSIONS
We conclude that endothelium-dependent vasorelaxation is impaired in long-term users of cocaine.
Havranek
E P
EP
Section of Cardiology, Denver General Hospital, Colorado 80204, USA.
Nademanee
K
K
Grayburn
P A
PA
Eichhorn
E J
EJ
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D003042:Cocaine / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014652:Vascular Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000009:adverse effects*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D003042:Cocaine; D000109:Acetylcholine