Dona M. Chikaraishi
Professor Emeritus of Neurobiology

Dr. Chikaraishi's laboratory studies the role of catecholamine neurotransmitters (dopamine, norepinephrine and epinephrine) during development. Catecholamine-deficient mice die at mid-gestation (E12.5), long before catecholamine neurons participate in neurotransmission, suggesting that catecholamines serve an unappreciated role in fetal survival.

Using physiological and pharmacological approaches, the laboratory has shown that catecholamines, particularly norepinephrine, maintain cardiovascular function in the fetus by regulating heart rate and contractility. This requirement is critical during hypoxia, which occurs throughout gestation due to spontaneous uterine contractions. Experimentally induced hypoxia preferentially kills catecholamine-deficient fetuses compared to wild type or heterozygous siblings in a time and dose-dependent manner. In vivo and in culture, hypoxia slows fetal heart rate and this bradycardia is exacerbated by blocking b1 adrenergic receptors. In isolated cultured hearts, where endogenous norepinephrine is absent, hypoxia also slows heart rate and this bradycardia can be reversed by activating b adrenergic receptors. It is likely that fetal survival is due to the cardiovascular requirement for b adrenergic activation because lethality of catecholamine-deficient animals is completely reversed by b adrenergic agonists administered via the pregnant dam.

The working hypothesis is that hypoxia reduces heart rate but also induces systemic norepinephrine release, which increases cardiac output via b adrenergic receptor activation. Restoration of cardiovascular function by norepinephrine allows the fetus to survive transient bouts of hypoxia in utero. Hence, catecholamines serve an acute and essential role in the fetus to maintain cardiovascular function. The critical catecholamine, norepinephrine, may act through a novel fetal b receptor to support survival.

Current Appointments & Affiliations

Contact Information

  • 2034 GSRB 1, 905 Lasalle, Durham, NC 27710
  • Box 103855 Med Ctr, Durham, NC 27710

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