Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study on rabbit aorta.
Effects of cocaine on vascular endothelium relaxing properties and the related mechanism were investigated in vitro in rabbit aorta. Several vasorelaxing agents with different mechanisms, i.e. acetylcholine, substance P, calcium ionophore A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprusside, were employed. Cocaine effects on the vascular response to relaxing agents in cumulative (acetylcholine, substance P, or A23187) or single dose (2,5-di-tert-butyl-hydroquinone) were performed in endothelium-intact aortic rings precontracted with phenylephrine. Relaxing activity of cumulative doses of sodium nitroprusside was evaluated in endothelium-denuded aortic rings, in the presence of cocaine. Cocaine significantly reduced endothelium-dependent relaxations induced by acetylcholine, or substance P. By contrast A23187 endothelium-mediated relaxation as well as endothelium-independent relaxation by sodium nitroprusside were unaffected by cocaine. Furthermore, cocaine significantly increased endothelium-dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic Ca2+-ATPase pump inhibitor, in the aortic rings. These findings indicate that cocaine reduces nitric oxide release from vascular endothelium apparently through the inhibiting action of Ca2+-ATPase pump.
Togna
G I
GI
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, P.le A. Moro, 5, 00185, Rome, Italy. giuseppina.togna@uniroma1.it
Graziani
M
M
Russo
P
P
Caprino
L
L
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D003042:Cocaine / Q000633:toxicity*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000633:toxicity*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D013373:Substance P; D000001:Calcimycin; D003042:Cocaine; D000109:Acetylcholine