Cocaine-stimulated endothelin-1 release is decreased by angiotensin-converting enzyme inhibitors in cultured endothelial cells.
OBJECTIVE
The primary aim was to determine the action of pathophysiologically relevant cocaine concentrations (10(-7)-10(-5) M) on endothelin-1 (ET-1) release from cultured endothelial cells under various cellular conditions. Further aims were to evaluate the effect of angiotensin-converting enzyme inhibitors on cocaine-treated endothelial cells, to assess their potential for inhibition of ET-1-stimulated release.


METHODS
Endothelin-1 release into the media was evaluated by radioimmunoassay under basal conditions and after 24 h treatment of endothelial cells with cocaine hydrochloride (HCl), or cocaine HCl and ACE inhibitors, captopril and lisinopril. The effect of serum and plasma under these conditions was also investigated.


RESULTS
Cocaine HCl stimulated ET-1 release in a dose response fashion that was independent of plasma or serum factors. Furthermore, cocaine-stimulated ET-1 release was inhibited by administration of angiotensin-converting enzyme inhibitors captopril and lisinopril.


CONCLUSIONS
These findings suggest that cocaine can directly stimulate endothelial cells to release ET-1 and that the observed increase is independent of serum or plasma factors. Furthermore, cocaine-stimulated endothelin-1 release appears to be mediated at least in part by the angiotensin system. These observations provide a framework for understanding the cellular mechanisms involved in cocaine-induced vasoconstriction.
Hendricks-Munoz
K D
KD
Neonatal Program, Department of Pediatrics, New York University Medical Center, NY 10016, USA.
Gerrets
R P
RP
Higgins
R D
RD
Munoz
J L
JL
Caines
V V
VV
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology; D011651:Pulmonary Artery; D013268:Stimulation, Chemical; D014471:Umbilical Veins
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D002216:Captopril; D017706:Lisinopril; D007770:L-Lactate Dehydrogenase; D003042:Cocaine