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Chronic prenatal hypoxia sensitizes β-adrenoceptors in the embryonic heart but causes postnatal desensitization

Department of Physics, Chemistry, and Biology (IFM), Division of Zoology, Linköping University, Linköping, Sweden

Submitted 20 March 2009 ; accepted in final form 19 May 2009

Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. β-Adrenoceptors (β-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac β-AR signaling and the incidence of alterations in the juvenile β-AR system due to the embryonic treatment. We measured functional β-AR density (B_max) through binding with [³H]CGP-12177 and the effect of agonists on β-AR-dependent contractility (pEC₅₀) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O₂) or chronic hypoxia (H, 14% O₂). Cardiac tissue from embryos and juveniles was used (15 and 19 day of embryonic development and 14 and 35 days posthatching, E19, E15, P14, and P35, respectively). Relative cardiac enlargement was found in the hypoxic groups at E15, E19, and P14, but not P35. B_max significantly decreased in E19H. B_max more than doubled posthatching but decreased from P14 to P35. The sensitivity to epinephrine was lower in E19N compared with E15N, but hypoxia increased the sensitivity to agonist in both E15H and E19H. Despite maintained receptor density, the P35H juvenile displayed a decreased sensitivity to β-AR agonist, something that was not seen in P14H. The postnatal decrease in β-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in β-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of β-AR signaling and may have important implications for cardiovascular function in the adult.

β-adrenergic; embryonic development; hypoxia; receptor density; receptor sensitivity