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Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival.

Publication ,  Journal Article
Portbury, AL; Chandra, R; Groelle, M; McMillian, MK; Elias, A; Herlong, JR; Rios, M; Roffler-Tarlov, S; Chikaraishi, DM
Published in: Am J Physiol Heart Circ Physiol
June 2003

Mice lacking catecholamines die before birth, some with cardiovascular abnormalities. To investigate the role of catecholamines in development, embryonic day 12.5 (E12.5) fetuses were cultured and heart rate monitored. Under optimal oxygenation, wild-type and catecholamine-deficient fetuses had the same initial heart rate (200-220 beats/min), which decreased by 15% in wild-type fetuses during 50 min of culture. During the same culture period, catecholamine-deficient fetuses dropped their heart rate by 35%. Hypoxia reduced heart rate of wild-type fetuses by 35-40% in culture and by 20% in utero, assessed by echocardiography. However, catecholamine-deficient fetuses exhibited greater hypoxia-induced bradycardia, reducing their heart rate by 70-75% in culture. Isoproterenol, a beta-adrenergic receptor (beta-AR) agonist, reversed this extreme bradycardia, restoring the rate of catecholamine-deficient fetuses to that of nonmutant siblings. Moreover, isoproterenol rescued 100% of catecholamine-deficient pups to birth in a dose-dependent, stereo-specific manner when administered in the dam's drinking water. An alpha-AR agonist was without effect. When wild-type fetuses were cultured with adrenoreceptor antagonists to create pharmacological nulls, blockade of alpha-ARs with 10 microM phentolamine or beta-ARs with 10 microM bupranolol alone or in combination did not reduce heart rate under optimal oxygenation. However, when combined with hypoxia, beta-AR blockade reduced heart rate by 35%. In contrast, the muscarinic blocker atropine and the alpha-AR antagonist phentolamine had no effect. These data suggest that beta-ARs mediate survival in vivo and regulate heart rate in culture. We hypothesize that norepinephrine, acting through beta-ARs, maintains fetal heart rate during periods of transient hypoxia that occur throughout gestation, and that catecholamine-deficient fetuses die because they cannot withstand hypoxia-induced bradycardia.

Duke Scholars

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

June 2003

Volume

284

Issue

6

Start / End Page

H2069 / H2077

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Survival
  • Receptors, Adrenergic, beta
  • Pregnancy
  • Organ Culture Techniques
  • Norepinephrine
  • Mice, Knockout
  • Mice, Inbred ICR
  • Mice
  • Hypoxia
 

Citation

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Chicago
ICMJE
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Portbury, A. L., Chandra, R., Groelle, M., McMillian, M. K., Elias, A., Herlong, J. R., … Chikaraishi, D. M. (2003). Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival. Am J Physiol Heart Circ Physiol, 284(6), H2069–H2077. https://doi.org/10.1152/ajpheart.00588.2002
Portbury, Andrea L., Rashmi Chandra, Marybeth Groelle, Michael K. McMillian, Alana Elias, James R. Herlong, Maribel Rios, Suzanne Roffler-Tarlov, and Dona M. Chikaraishi. “Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival.Am J Physiol Heart Circ Physiol 284, no. 6 (June 2003): H2069–77. https://doi.org/10.1152/ajpheart.00588.2002.
Portbury AL, Chandra R, Groelle M, McMillian MK, Elias A, Herlong JR, et al. Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival. Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2069–77.
Portbury, Andrea L., et al. “Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival.Am J Physiol Heart Circ Physiol, vol. 284, no. 6, June 2003, pp. H2069–77. Pubmed, doi:10.1152/ajpheart.00588.2002.
Portbury AL, Chandra R, Groelle M, McMillian MK, Elias A, Herlong JR, Rios M, Roffler-Tarlov S, Chikaraishi DM. Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival. Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2069–H2077.

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

June 2003

Volume

284

Issue

6

Start / End Page

H2069 / H2077

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Survival
  • Receptors, Adrenergic, beta
  • Pregnancy
  • Organ Culture Techniques
  • Norepinephrine
  • Mice, Knockout
  • Mice, Inbred ICR
  • Mice
  • Hypoxia