Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in uninephrectomized adult male sheep.

Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1-7) in rams and the angiotensin receptors involved in mediating responses to the peptide. Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1-7) infusions (1 ng/kg/min) alone or in combination with antagonists to angiotensin receptors for 3 h.

A specific CRH antagonist attenuates ACTH-stimulated cortisol secretion in ovine adrenocortical cells.

Corticotropin releasing hormone (CRH) has been detected in the adrenal gland of many species and may be involved in regulation of glucocorticoid secretion. In cultured human fetal adrenal definitive/transitional zone cells, CRH upregulates the adrenocorticotropic hormone (ACTH) receptor and steroidogenic enzymes and is blocked by the selective CRH type 1 receptor (CRH(1)) antagonist, antalarmin. Based on these findings and evidence that antalarmin infusion into sheep suppressed prepartum increases in cortisol, we hypothesized that antalarmin would influence adrenal cortisol secretion.

Fetal and postnatal renin secretion in female sheep exposed to prenatal betamethasone.

Prenatal glucocorticoids have long-term effects on the kidney and blood pressure that may be mediated by the renin-angiotensin system (RAS). We studied the effects of antenatal betamethasone administration on renin in fetal and adult female sheep. Pregnant sheep received 2 doses of betamethasone or vehicle, at 80 and 81 days of gestation (dGA).

Plasma and renal renin concentrations in adult sheep after prenatal betamethasone exposure.

This study examined whether renin expression and secretion and plasma angiotensin II (Ang II) levels were altered in adult sheep exposed to antenatal betamethasone. Pregnant sheep received injections of 0.17 mg/kg betamethasone or vehicle, at 80 and 81 days of gestation, and offspring were studied at 6 and 18 months of age.

Thyroid hormone regulates renocortical COX-2 and PGE2 expression in the late gestation fetal sheep.

Cyclooxygenase 2 (COX-2) is important for development of the fetal kidney. Precisely how renal COX-2 expression is regulated in fetal life is unclear. The hypothesis that thyroid hormone positively regulates COX-2 and PGE(2) levels in the late gestation fetal kidney cortex was tested.

Thyroid hormone replacement normalizes renal renin and angiotensin receptor expression in thyroidectomized fetal sheep.

Previous studies have suggested that thyroid hormone influences maturation of the renin-angiotensin system (RAS) and cardiovascular function in the late-gestation fetal sheep. To further examine the importance of thyroid hormone in this regard, we used the technique of thyroidectomy (TX) to remove endogenous thyroid hormone from the circulation and then replaced it with physiological amounts of exogenous thyroxine. We hypothesized that the previously observed changes in RAS activity and cardiovascular function associated with TX would be normalized.

Combined thyroidectomy and renal denervation suppress renin expression and secretion in fetal sheep.

Background And Objectives: 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.

Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep.

The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness.

Ontogeny and effects of thyroid hormone on beta1-adrenergic receptor mRNA expression in ovine fetal kidney cortex.

Objective: Previous studies indicate that thyroidectomy (TX) decreases renin gene expression in ovine fetal renal cortex in late gestation. Fetal ovine renin-containing renocortical cells become increasingly responsive to beta-adrenergic stimulation as gestation proceeds. Increases in plasma thyroid hormone concentrations parallel this change, suggesting that there is a positive developmental relationship between the two.

Developmental changes in adrenocorticotrophin (ACTH)-induced expression of ACTH receptor and steroid acute regulatory protein mRNA in ovine fetal adrenal cells.

Objectives: Adrenocorticotrophin (ACTH) plays an important role in mediating the increase in cortisol output in the late gestation sheep fetus. At the adrenal itself, heightened expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) appear to be important parallel changes. This study examined how ACTH affects ACTH-R and StAR mRNA expression, and cortisol production in adrenocortical cells isolated from fetuses of varying gestational age (dGA).

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep.

Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward 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.

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression.

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling.

The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep.

The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known.

The role of hypothalamic input on corticotroph maturation in fetal sheep.

Corticotropin-releasing hormone receptor type 1 (CRH-R1) expression and vasopressin type 1b (V1b) receptor protein decrease in late-gestation fetal sheep. Because hypothalamo-pituitary disconnection (HPD) has been demonstrated to prevent the morphological maturation of corticotrophs, we hypothesized that hypothalamic input is necessary for the maturational changes in CRH-R1 and V1b receptor levels. We measured CRH-R1 and V1b receptor expression in the anterior pituitaries of fetuses at 140 days gestational age (dGA) that underwent HPD or sham surgery at 120 dGA.

Inhibition of cyclooxygenase-2: effects on renin secretion and expression in fetal lambs.

The importance of prostaglandins in the regulation of the renin-angiotensin system during development is not known. These experiments were conducted to examine the effects of prostaglandin synthesis inhibitors on basal and isoproterenol-induced plasma renin concentration and renin gene expression in the late-gestation fetal lamb. Eighteen lamb fetuses ranging in gestational age from 129 to 138 days underwent surgical insertion of femoral arterial and venous catheters under general endotracheal anesthesia.