Prenatal cocaine exposure affects the development of aortic adrenergic innervation and contractile responses.
This study examines the effects of prenatal cocaine administration on the development of vascular sympathetic innervation and contractile responsiveness. Rabbits received cocaine (4 mg/kg, iv, bid) or saline during gestational days 8 to 29. Aortas were obtained on postnatal days 10, 20, 30 and 50. Vascular smooth muscle responsiveness was assessed by measuring aortic contractile responses to norepinephrine (NE) and to other vasoconstrictors. Vascular adrenergic innervation was evaluated by measuring desipramine sensitive [3H]-NE uptake into aortic ring segments and aortic NE content. [3H]-NE uptake and NE content were reduced at postnatal days 10 and 20 in the rabbits exposed prenatally to cocaine. Differences were not observed at postnatal days 30 or 50. The contractile response to NE was reduced in rabbits exposed to cocaine prenatally. Maximal response and potency were decreased at postnatal day 10 and potency was still decreased at day 20, but not at the older ages. Contractile responses to serotonin (5-HT) and angiotensin II (AII) were not affected by prenatal cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of aortic adrenergic innervation and alpha adrenoceptor responsiveness.
Johnson
M D
MD
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Gurdal
H
H
Cai
G
G
Snyder
D L
DL
Roberts
J
J
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000294:innervation / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000294:innervation* / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000196:embryology / Q000254:growth & development*; D014316:Tritium
D014316:Tritium; D000804:Angiotensin II; D012701:Serotonin; D003042:Cocaine; D009638:Norepinephrine