title: Consequences of maternal cocaine on cerebral microvascular functions in piglets.
abstract: Maternal cocaine abuse is associated with fetal and neonatal neurological abnormalities. Prolonged exposure to cocaine can induce blood flow disorders, growth restriction, and hypoxia in the newborn. We investigated the impact of chronic fetal cocaine exposure on cerebral microvascular reactivity and autonomic function in the piglets. Pregnant pigs received cocaine (1 mg/kg i.v.; twice weekly) or saline throughout the last trimester. Prenatal exposure to cocaine did not have any significant effect on the birth weight of the piglets as compared to the control. Following delivery, effects of recurrent prenatal cocaine exposure on cerebral microvascular functions were examined in piglets (3-6 days old). Pial arteriolar responses to applications of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), and clonidine were examined using closed cranial windows. Functional effects of prenatal cocaine exposure on changes in mean arterial pressure (MAP) and pial arteriolar diameter induced by intracisternal injection (i.c.) of clonidine (1 microg/kg) were also determined. Topical applications of 5-HT, ET-1, and clonidine dose-dependently decreased pial arteriolar diameter in the control and these constrictions were significantly enhanced in the in utero cocaine-exposed piglets. Prenatal cocaine exposure did not have any significant effects on the resting MAP and heart rate as there were no differences between the groups. IC clonidine caused sustained decrease in MAP in both groups but the decrease was more pronounced in the cocaine than the control group. IC clonidine causes cerebral microvascular dilation coincident with the development of hypotension. Such dilation was severely attenuated in the cocaine group, even though the hypotension was much more pronounced than in the control. In conclusion, prenatal cocaine exposure resulted in attenuated autoregulatory vasodilation and potentiated responses to vasoconstrictor agents. The mechanisms behind the effects of in utero cocaine exposure on alteration of newborn cerebral functions need further investigation. Such actions may be important in development of cerebral pathologies associated with recurrent prenatal cocaine exposure.
authors.affiliation: Laboratory for Research in Neonatal Physiology, Vascular Biology Program, Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. yakuba_ma@tsu.edu
authors.forename: Momoh A
authors.initials: MA
authors.lastname: Yakubu
authors.forename: Massroor
authors.initials: M
authors.lastname: Pourcyrous
authors.forename: Mildred M
authors.initials: MM
authors.lastname: Randolph
authors.forename: Kari E
authors.initials: KE
authors.lastname: Blaho
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Mandrell
authors.forename: Henrietta S
authors.initials: HS
authors.lastname: Bada
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D001341:Autonomic Nervous System / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D003042:Cocaine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005333:Fetus; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010841:Pia Mater / Q000098:blood supply*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D013552:Swine; D013565:Sympatholytics / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D013565:Sympatholytics; D014662:Vasoconstrictor Agents; D012701:Serotonin; D003042:Cocaine; D003000:Clonidine