Premium
Postnatal β‐adrenergic desensitization caused by chronic prenatal hypoxia is linked to an increase in Gs and decreased β1AR/β2AR ratio
Author(s) -
Lindgren Isa Maria,
Altimiras Jordi
Publication year - 2011
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.25.1_supplement.858.15
Subject(s) - desensitization (medicine) , hypoxia (environmental) , adrenergic , medicine , chemistry , endocrinology , receptor , oxygen , organic chemistry
Prenatal hypoxia leads to growth restriction and increased risk of adult cardiovascular disease. Additionally, it desensitizes βARs in the 5wk chicken heart without affecting the 2wk heart. β 1 AR/β 2 AR ratio and increased G i expression is related to decreased βAR sensitivity. Our objective was to determine if the observed decrease in βAR sensitivity in the prenatally hypoxic 5 week chicken heart is linked to changes in β 1 AR/β 2 AR ratio, G i expression and cAMP accumulation. Eggs incubated in normoxia (N, 20.95% O 2 ) or hypoxia from day 0 (H, 14% O 2 ) were hatched and raised to 5wks. The β 1 AR/β 2 AR ratio was assessed in heart slices by competitive binding of [ 3 H]CGP‐12177 and specific β 1 AR or β 2 AR blockers (CGP‐20712A and ICI‐118,551 respectively). G s and G i expression was assessed by Western blot and an immunoassay was used to determine the cAMP accumulation after βAR stimulation with isoproterenol. We found that prenatal hypoxia causes a decrease in β 1 AR/β 2 AR ratio and lower cAMP levels in H than N. However, G i was unchanged while G s was increased. In conclusion, the results of lower β 1 AR/β 2 AR ratio, increased G s expression and lower cAMP production following βAR stimulation resemble those reported in early human heart failure. We therefore 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.