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Prenatal hypoxia programs adult cardiac contractile dysfunction through changes in beta‐adrenergic signaling
Author(s) -
Lindgren Isa,
Holm AnnCharlotte B Svensson,
Altimiras Jordi
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1187.2
Subject(s) - contractility , hypoxia (environmental) , stimulation , endocrinology , medicine , desensitization (medicine) , adrenergic , adrenergic receptor , fetus , cardiac function curve , biology , receptor , heart failure , chemistry , pregnancy , genetics , organic chemistry , oxygen
Prenatal hypoxia leads to fetal growth restriction and increased risk of adult cardiovascular disease. We have previously shown that adult cardiac beta‐adrenergic receptor (βAR) desensitization is programmed by prenatal hypoxia. Our objective was to determine how the observed βAR desensitization affects cardiac contractility in vivo and whether it is linked to changes in cAMP accumulation, β1AR/β2AR ratio or G‐protein expression. Eggs were incubated in normoxia (N, 20.95% O2) or hypoxia from day 0 (H, 14% O2), hatched and raised to 5wks of age. Echocardiograms were recorded in anesthetized birds before and after isoproterenol stimulation. cAMP accumulation in isolated cells after stimulation with isoproterenol, β1AR/β2AR ratio and Gs and Gi expression in tissue was also assessed. Prenatal hypoxia caused contractile dysfunction as shown by a decrease in systolic diameter. cAMP levels after βAR stimulation and β1AR/β2AR ratio were lower in hypoxic incubated birds. Gi expression was unchanged while Gs was increased. Our results resemble those reported in early human heart failure. We conclude that prenatal hypoxia has a programming effect on adult βAR function and speculate that the 5 week chicken exposed to prenatal hypoxia is displaying early signs of heart failure. Supported by FORMAS Centre of Excellence in Animal Welfare Science and career grant from Linköpings universitet to JA.