Combined thyroidectomy and renal denervation suppress renin expression and secretion in fetal sheep.
OBJECTIVE
Activity of the fetal renin-angiotensin system (RAS) is developmentally regulated, increasing in late gestation toward term. Thyroid hormone and the renal nerves are both important modulators of renal RAS maturation; however, ablation of either influence alone does not totally block the aforementioned developmental late gestation increase in RAS in fetal sheep. In the current study, we used the technique of thyroidectomy combined with bilateral renal denervation (TX+D), which removes thyroid hormone from the circulation and abolishes effects of renal nerve activity, to determine if simultaneous removal of their effects on the kidney would markedly alter renin expression and secretion in late gestation.


METHODS
TX+D was performed at 120 days of gestation age (dGA). Control fetuses were sham-operated. Immediately before necropsy (approximately 138 dGA), fetuses were infused with isoproterenol to examine plasma active and prorenin changes in response to beta-adrenergic stimulation.


RESULTS
TX+D decreased plasma thyroid hormone concentrations, renal renin mRNA, renal active and prorenin levels, and plasma active and prorenin concentrations. Isoproterenol-induced increases in plasma active renin were also reduced in TX+D fetuses. TX+D did not alter renal angiotensin (Ang) II subtype receptor (AT2) expression close to term.


CONCLUSIONS
These findings suggest that TX+D synergize in the suppression of fetal renin expression.
Chen
Kai
K
Department of Obstetrics/Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1066, USA.
Carey
Luke C
LC
Valego
Nancy K
NK
Liu
Jingfang
J
Rose
James C
JC
D000818:Animals; D003714:Denervation; D005260:Female; D005865:Gestational Age; D007668:Kidney / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D012083:Renin / Q000096:biosynthesis*; D012084:Renin-Angiotensin System / Q000502:physiology; D012756:Sheep; D013963:Thyroid Hormones / Q000096:biosynthesis; D013965:Thyroidectomy
D013963:Thyroid Hormones; D012083:Renin