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

Lindgren I, Altimiras J. Chronic prenatal hypoxia sensitizes beta-adrenoceptors in the embryonic heart but causes postnatal desensitization. Am J Physiol Regul Integr Comp Physiol 297: R258-R264, 2009. First published May 20, 2009; doi:10.1152/ajpregu.00167.2009.-Prenatal hypoxia in mammals causes fetal growth restriction and catecholaminergic overstimulation that, in turn, alter signaling pathways associated with adrenergic receptors. beta-Adrenoceptors (beta-ARs) are essential for fetal cardiac development and regulation of cardiac contractility. We studied the effects of chronic prenatal hypoxia on cardiac beta-AR signaling and the incidence of alterations in the juvenile beta-AR system due to the embryonic treatment. We measured functional beta-AR density (B-max) through binding with [H-3]CGP-12177 and the effect of agonists on beta-AR-dependent contractility (pEC(50)) through concentration-response curves to epinephrine. Eggs from broiler chickens were incubated in normoxia (N, 21% O-2) or chronic hypoxia (H, 14% O-2). 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. Bmax 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 beta-AR agonist, something that was not seen in P14H. The postnatal decrease in beta-AR sensitivity as an effect of chronic prenatal hypoxia, without a concomitant change in beta-AR density, leads us to conclude that the embryonic hypoxic challenge alters the future progression of beta-AR signaling and may have important implications for cardiovascular function in the adult.