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Postnatal‐related changes in cAMP mediated pulmonary arterial relaxation and calcium signals persist following long term hypoxia in sheep
Author(s) -
Paez Ricardo,
Rubalcava Monica,
Blood Quintin,
Hong Sam,
Francis Michael,
Taylor Mark S,
Longo Lawrence D,
Wilson Sean M
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.1140.6
Subject(s) - ibmx , electrical impedance myography , fetus , medicine , hypoxia (environmental) , vasodilation , endocrinology , phosphodiesterase , calcium , phosphodiesterase inhibitor , chemistry , biology , stimulation , pregnancy , oxygen , organic chemistry , biochemistry , forskolin , genetics , enzyme
Phosphodiesterase (PDE) inhibition can elevate cAMP, dilate pulmonary arteries (PA) and is a therapeutic target for persistent pulmonary hypertension of the newborn. To test whether long term hypoxia (LTH) impairs postnatal maturation of cAMP‐mediated vasodilation and associated Ca 2+ signals we reduced cAMP degradation by treating PAs with a non‐selective PDE inhibitor (IBMX). Wire‐myography and confocal Ca 2+ imaging were performed on PA isolated from fetal, newborn, or adult sheep that lived at low (720 m) or high altitude (3,801 m) for >;100 days. IBMX caused a dose‐dependent relaxation of serotonin‐constricted PA from all groups and reduced Ca 2+ wave amplitude as well as other spatial and temporal components to the Ca 2+ signals in newborns but not in fetuses. In arteries from adult normoxic sheep, IBMX impaired spatial and temporal Ca 2+ signals. Yet, IBMX also reduced Ca 2+ wave amplitude in arteries of LTH adults. LTH increased Ca 2+ wave amplitudes in newborns and modified spatial and temporal components to the waves, but failed to alter signals in the fetus. With regards to development, Ca 2+ wave amplitudes were elevated in the newborn relative to the fetus and the adult, while spatial and temporal aspects were unchanged. These results suggest that cAMP dilates immature and adult pulmonary arteries, in part, by depressing Ca 2+ signals. NSF MRI923559, NIH R03HD69746, R01HD31226, R01HD3807, P20MD6988