Propranolol blocks cocaine-induced cerebral vasodilation in newborn sheep.
OBJECTIVE
The objective of this study was to test the hypothesis that cocaine-induced cerebral vasodilation in newborn sheep is mediated via beta-adrenergic receptor activation.


METHODS
The cerebral effects of a single intravenous injection of cocaine (4 mg/kg) given 30 mins after pretreatment with propranolol (1 mg/kg) were studied and compared with the results from a previous study using an identical cocaine protocol without propranolol pretreatment.


METHODS
Seven chronically catheterized, unanesthetized newborn sheep (6 +/- 1 days old).


METHODS
Cerebral blood flow using radiolabeled microspheres, mean arterial blood pressure (MAP), heart rate, and cerebral arterial and venous oxygen content were measured at baseline, after administration of propranolol, and 0.5, 5, 15, and 60 mins after cocaine injection. Cerebrovascular resistance was calculated as the MAP divided by the cerebral blood flow.


RESULTS
Propranolol injection alone caused no systemic or cerebral physiologic changes other than an 11 +/- 2% (mean +/- SEM) decrease in heart rate, which was sustained after cocaine injection. In contrast to previous studies showing cerebral vasodilation (25% decrease in cerebrovascular resistance) and acute hypertension (57% increase in MAP) 30 secs after cocaine injection, there were no changes in cerebrovascular resistance after cocaine injection and after propranolol pretreatment and there was only a 23 +/- 7% increase in MAP 30 secs after injection, with a return to baseline by 15 mins. Cocaine and norepinephrine levels were similar to those previously reported in the newborn sheep after an injection of 4 mg/kg cocaine.


CONCLUSIONS
Propranolol blocks cocaine-induced cerebral vasodilation and blunts the acute hypertension in newborn sheep, suggesting that cocaine's cerebrovascular effects in the developing brain are mediated, at least in part, by beta-adrenergic receptor activation.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000150:complications*; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D011433:Propranolol / Q000627:therapeutic use*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects