| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-adrenergic receptor to maintain fatal heart rate and survival
1 Department of Neurobiology, Duke University Medical Center, Durham, NC, USA
2 Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
3 Department of Neuroscience, Tufts University Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: donam{at}neuro.duke.edu.
Mice lacking catecholamines die before birth, some with cardiovascular abnormalities. To investigate the role of catecholamines in development, 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 per minute), which decreased by 15% in wild type fetuses during 50 minutes 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 
-adrenergic receptor (AR) agonist, reversed this extreme bradycardia, restoring the rate of catecholamine-deficient fetuses to that of non-mutant siblings. Moreover, isoproterenol, in a dose-dependent, stereo-specific manner, rescued 100% of catecholamine-deficient pups to birth when administered in the drinking water of the pregnant dam. An 
AR agonist was without effect.
When wild type fetuses were cultured with adrenoreceptor antagonists to create pharmacological nulls, blockade of ARs (with 10 µM phentolamine) or ARs with (10 µM bupranolol) alone or in combination did not reduce heart rate under optimal oxygenation. However, when combined with hypoxia, AR blockade reduced heart rate by 35%. In contrast, the muscarinic blocker, atropine, and the AR antagonist, phentolamine, had no effect. These data suggest that adrenergic receptors mediate survival in vivo and regulate heart rate in culture. We hypothesize that norepinephrine, acting through 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.
This article has been cited by other articles:
|
|
 |
|
  Y. Morikawa and P. Cserjesi Cardiac Neural Crest Expression of Hand2 Regulates Outflow and Second Heart Field Development Circ. Res., December 5, 2008; 103(12): 1422 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Ream, R. Chandra, M. Peavey, A. M. Ray, S. Roffler-Tarlov, H.-G. Kim, W. C. Wetsel, H. A. Rockman, and D. M. Chikaraishi High oxygen prevents fetal lethality due to lack of catecholamines Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R942 - R953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ream, A. M. Ray, R. Chandra, and D. M. Chikaraishi Early fetal hypoxia leads to growth restriction and myocardial thinning Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R583 - R595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Menheniott, K. Woodfine, R. Schulz, A. J. Wood, D. Monk, A. S. Giraud, H. S. Baldwin, G. E. Moore, and R. J. Oakey Genomic Imprinting of Dopa decarboxylase in Heart and Reciprocal Allelic Expression with Neighboring Grb10 Mol. Cell. Biol., January 1, 2008; 28(1): 386 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Ebert and D. G. Taylor Catecholamines and development of cardiac pacemaking: An intrinsically intimate relationship Cardiovasc Res, December 1, 2006; 72(3): 364 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chalothorn, H. Zhang, J. A. Clayton, S. A. Thomas, and J. E. Faber Catecholamines augment collateral vessel growth and angiogenesis in hindlimb ischemia Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H947 - H959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Huang, J. J. Bahl, Y. Wu, F. Hu, D. F. Larson, W. R. Roeske, and G. A. Ewy Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H497 - H503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. S. Li, T. D. Pham, H. Tamir, J. J. Chen, and M. D. Gershon Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation J. Neurosci., February 11, 2004; 24(6): 1330 - 1339. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
