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1 Obstetrics/Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
2 Physiology/Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
3 Obstetrics/Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Physiology/Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
* To whom correspondence should be addressed. E-mail: jimrose{at}wfubmc.edu.
Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation towards term. At the same time fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately prior to necropsy (around 137 dGA) fetuses were infused with isoproterenol and the hemodynamic responses noted. TX significantly decreased plasma thyroid hormone concentrations, renal renin mRNA and renal active renin levels, but did not change fetal plasma active renin levels. TX decreased both AT1 mRNA and protein levels in kidney and lung, but not in the left ventricle. TX was also associated with increased AT2 mRNA and protein at the 44 kD band in kidney, while AT2 protein was decreased at the 78 kD level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late gestation fetal sheep.
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