Reduction of uterine blood flow by phenylephrine, an alpha-adrenergic agonist, in the day 11 pregnant rat: relationship to potentiation of acetazolamide teratogenesis.
We have demonstrated previously that phenylephrine, a selective postsynaptic alpha-1-adrenergic agonist, significantly potentiates the incidence of acetazolamide-induced right forelimb ectrodactyly in a dose-response manner. As reported herein, phenylephrine also decreases maternal uterine blood flow in a dose-response manner as measured by radioactive microsphere methodology. At the potentiative dose of 12.5 mg/kg phenylephrine decreases uterine blood flow by 86.8% when compared to control. In turn, pretreatment with prazosin, a selective postsynaptic alpha-1-adrenergic antagonist, prevents this large decrease in uterine blood flow and abolishes the potentiation of acetazolamide teratogenesis by phenylephrine. Although the effects of acetazolamide or acetazolamide + phenylephrine on uterine blood flow were not measured the data suggest a correlation between decreased uterine blood flow and potentiation of acetazolamide teratogenesis.
Ugen
K E
KE
Children's Hospital Research Foundation, Cincinnati, Ohio.
Scott
W J
WJ
D000086:Acetazolamide / Q000633:toxicity*; D000818:Animals; D004357:Drug Synergism; D005260:Female; D005552:Forelimb / Q000002:abnormalities; D010656:Phenylephrine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013723:Teratogens; D014599:Uterus / Q000098:blood supply / Q000187:drug effects*
D013723:Teratogens; D010656:Phenylephrine; D000086:Acetazolamide