Effects of cocaine, benzoylecgonine, and cocaine metabolites in cannulated pressurized fetal sheep cerebral arteries.
Prenatal cocaine exposure has been reported to cause neurovascular complications in the developing fetus. To determine the effect of cocaine on the fetal neurovasculature, we studied the in vitro response of fetal sheep cerebral arteries to cocaine and cocaine metabolites. The change in diameter of cannulated pressurized cerebral artery segments from fetal sheep was measured using a video microscaler system. Cumulative dose-response curves (10(-12)-10(-4) M) were generated for cocaine and the major cocaine metabolites in fetal sheep cerebral artery segments. Benzoylecgonine (> 10(-10) M) also caused concentration-dependent constriction, and cerebral artery segments were significantly more sensitive to benzoylecgonine than to cocaine and the other cocaine metabolites. Benzoylecgonine-induced vasoconstriction appeared to be mediated through alpha-adrenergic stimulation, predominantly through stimulation of alpha 1-adrenergic receptor subtypes. We conclude that cocaine and benzoylecgonine cause significant fetal cerebral artery vasoconstriction in vitro. Cocaine and benzoylecgonine-induced cerebral vasoconstriction may contribute to the perinatal neurovascular complications associated with prenatal cocaine exposure.
Schreiber
M D
MD
Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Madden
J A
JA
Covert
R F
RF
Torgerson
L J
LJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D002536:Cerebral Arteries / Q000187:drug effects* / Q000196:embryology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; C008671:norcocaine; C005618:benzoylecgonine; C005617:ecgonine; D003042:Cocaine