Effect of chronic cocaine exposure on carotid artery reactivity in neonatal rabbits.
Chronic cocaine abuse by pregnant women results in chronic neonatal drug exposure. In adults, chronic cocaine use alters neurotransmitter concentrations and receptor dose-response relationships. Similar changes may also occur in the neonatal cerebrovasculature after in utero cocaine exposure. This study examined the effect of chronic cocaine exposure on internal carotid artery reactivity to norepinephrine, serotonin, acetylcholine, sodium nitroprusside, adenosine, and cocaine in neonatal rabbits. Internal carotid artery rings were isolated from 16 to 20 day old rabbits that had received cocaine (20 mg/kg IP BID, n = 8) or saline (n = 8) from 5 days of age and were studied in organ baths using standard in vitro techniques. Chronic treatment with cocaine decreased the half-maximal relaxant response (ED50) to adenosine (control 6.9 +/- 1.8 vs cocaine 3.5 +/- 0.99 microM, p = 0.05). The half-maximal contractile responses (EC50) to norepinephrine and serotonin and the half-maximal relaxant responses (ED50) to acetylcholine and sodium nitroprusside were similar between groups. The threshold concentration of cocaine that induced vessel contraction was altered by chronic cocaine exposure (control group 10(-6) M vs chronic cocaine group 10(-4) M). We conclude that chronic cocaine exposure sensitizes carotid arteries to the relaxant effects of adenosine. In addition, chronic cocaine exposure desensitizes carotid arteries to the contractile effects of acute cocaine. These vasoreactivity changes may underlie altered cerebrovascular responses to asphyxia and play a role in the pathogenesis of postnatally acquired brain injury in critically ill "crack" babies.
O'Rourke
M M
MM
Department of Anesthesiology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Loeb
A L
AL
Feuer
P
P
Monitto
C L
CL
Kurth
C D
CD
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002339:Carotid Arteries / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
D012701:Serotonin; D003042:Cocaine; D000241:Adenosine; D000109:Acetylcholine; D009638:Norepinephrine