Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine.
Previous studies in pregnant ewes have demonstrated that intravenous (IV) cocaine produces increased maternal blood pressure and vasoconstriction of the uterine arteries, resulting in decreased uterine blood flow and decreased fetal oxygen levels. To determine whether these responses to cocaine were mediated by alpha 1-adrenergic receptor stimulation, cocaine was administered to four pregnant ewes before and after phenoxybenzamine hydrochloride, an alpha 1 receptor antagonist. Before phenoxybenzamine infusion, cocaine 2.0 mg/kg produced a 53% increase in maternal mean arterial pressure (MAP), a 50% reduction in total uterine blood flow, and a 191% increase in uterine vascular resistance. Cocaine also increased fetal MAP by 24%, increased the fetal heart rate (FHR) by 51%, and reduced fetal PO2 by 29%. Alpha 1 receptor blockade after phenoxybenzamine 5.0 mg/kg was confirmed by a lack of change in uterine blood flow to IV norepinephrine 30 micrograms before cocaine administration. After phenoxybenzamine, cocaine produced no increase in maternal or fetal MAP. However, total uterine blood flow decreased 44%, uterine vascular resistance increased 59%, FHR increased 36%, and fetal PO2 fell 18%. Because the fetal responses mimicked the maternal responses to cocaine both before and after phenoxybenzamine, phenoxybenzamine apparently crossed the placenta to block fetal alpha 1 receptors as well. Alpha 1-adrenergic receptor stimulation is the major mechanism for the maternal and fetal hypertensive responses to cocaine. Although cocaine produces uterine artery vasoconstriction primarily by alpha 1 adrenergic receptor stimulation, its vasoconstrictive effects may involve other vasoactive neurotransmitters, such as dopamine or serotonin.
Dolkart
L A
LA
Department of Obstetrics and Gynecology, University of Rochester, School of Medicine and Denistry, New York.
Plessinger
M A
MA
Woods
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000032:analysis / Q000187:drug effects; D005318:Fetal Heart / Q000187:drug effects; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000097:blood; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply; D014655:Vascular Resistance
D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D002245:Carbon Dioxide; D003042:Cocaine; D010100:Oxygen