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Glucocorticoids are administered for preterm labor to improve postnatal adaptation. We assessed the effect of antenatal betamethasone (Beta) treatment on preterm newborn lamb neuroendocrine [catecholamine, arginine vasopressin (AVP)] and endocrine [triiodothyronine (T(3)), ANG II, and atrial natriuretic factor (ANF)] adaptive responses following delivery and a hypoxic challenge. Beta treatment included direct fetal injection at 0.2 (F(0.2); n = 8) or 0.5 (F(0.5); n = 7) mg/kg estimated fetal body weight or maternal injection with 0.2 (n = 8) or 0.5 mg/kg (M(0.5); n = 8). Control animals received fetal and maternal intramuscular injections of saline (n = 8). After 24 h, lambs were delivered by cesarean section, surfactant treated, and ventilated for 4 h. Relative to the control lambs, 3 h after delivery, there was a marked suppression of plasma cortisol, epinephrine, norepinephrine, and ANG II levels and elevated plasma T(3) and ANF levels, systolic blood pressure, and left ventricular contractility (dP/dt; F(0.5) and M(0.5)) values in F(0.5) and both maternal Beta-treated groups. However, Beta treatment augmented the cardiac output, cortisol, norepinephrine, AVP, and ANF responses to 20 min of hypoxia (PO(2) = 25-30 mmHg). We concluded that short-term (24 h) antenatal glucocorticoid exposure 1) alters preterm newborn postnatal blood pressure regulation in the face of marked depression of plasma cortisol, catecholamine, and ANG II levels and 2) augments the postnatal neuroendocrine and endocrine responses to a hypoxic challenge.

We assessed renal and cardiovascular function in preterm newborn lambs after antenatal glucocorticoid exposure. Pregnant ewes were randomly assigned to receive betamethasone or saline via either direct fetal or maternal injection at 122 d gestation. Lambs were delivered 15 h later, and cardiovascular and renal function was assessed. Two hours after delivery, baseline urine flow, urinary sodium excretion, and urinary osmolar clearance were similar in all groups. Volume expansion (saline, 2.5% of body weight, for 10 min) increased values for urine flow (0.23 +/- 0.04 to 0.58 +/- 0.09 mL x min(-1) x kg(-1)), urinary sodium excretion (29.7 +/- 5.8 to 76.2 +/- 12.3 microEq x min(-1) x kg(-1)), and osmolar clearance (12.2 +/- 1.2 to 24.3 +/- 1.6 mL/100 mL GFR) in the fetal group. Increases in urine values were also observed in the maternal group, but control values did not change significantly. Mean arterial pressure was increased in both betamethasone-treated groups relative to controls. Short-term antenatal betamethasone exposure 1) augments preterm newborn kidney adaptive responses to acute volume expansion, and 2) increases postnatal blood pressure in preterm newborn lambs.

We evaluated postnatal lung function and intravascular albumin loss to tissues of 123-days-gestation preterm surfactant-treated and ventilated lambs 15 h after direct fetal (n = 8) or maternal (n = 9) betamethasone treatment or saline placebo (n = 9). The betamethasone-treated groups had similar increases in dynamic compliances, ventilatory efficiency indexes, and lung volumes relative to controls (P < 0.05). The losses of 125I-labeled albumin from blood, a marker of intravascular integrity, and the recoveries of 125I-albumin in muscle and brain were similar for control and betamethasone-exposed lambs. Betamethasone-treated lambs had lower recoveries of 125I-albumin in lung tissues and in alveolar washes than did controls (P < 0.01). Although blood pressures were higher for the treated groups (P < 0.05), all groups had similar blood volumes, cardiac outputs, and organ blood flows. Maternal or fetal treatment with betamethasone 15 h before preterm delivery equivalently improved postnatal lung function, reduced albumin recoveries in lungs, and increased blood pressures. However, prenatal betamethasone had no effects on the systemic intravascular losses of albumin or did not change blood volumes.

Unlabelled: These studies determined the effects of fetal treatment with betamethasone alone, or in combination with thyroid hormone (thyroxine; T4), on postnatal renal and endocrine adaptations in preterm newborn lambs. Ovine fetuses (126 d of gestation; term = 150 d) received single, ultrasound-guided intramuscular injections of saline, 0.5 mg/kg betamethasone (Celestone Soluspan, or 0.5 mg/kg betamethasone plus 60 micrograms/kg T4. After 48 h, lambs were delivered, treated with surfactant (Survanta, 100 mg/kg), and ventilated for 3 h. Due to maintained urine flow in the betamethasone-treated animals and a significant decrease in the saline group, betamethasone versus saline urine flow values (0.11 +/- 0.03 versus 0.03 +/- 0.004 mL.min-1.kg-1) were significantly elevated by the end of studies. GFR (1.5 +/- 0.3 versus 0.8 +/- 0.2 mL.min-1.kg-1) and mean blood pressure (61 +/- 4 versus 42 +/- 3 mm Hg) values also were higher in the betamethasone-treated animals. Although renal blood flow, renal plasma flow, and fractional sodium excretion rates did not differ, betamethasone versus saline values for the filtration fraction (11.9 +/- 1.5 versus 7.4 +/- 1.5%) and total sodium reabsorption (196 +/- 38 versus 81 +/- 16 microEq.min-1.kg-1) were increased. Betamethasone versus saline treatment also was associated with significant reductions in plasma angiotensin II (125 +/- 23 versus 550 +/- 140 pg/mL) and AVP (116 +/- 19 versus 230 +/- 77 pg/mL) levels. Overall, the effects of combined betamethasone + T4 treatment were similar to the effects of betamethasone alone., Conclusions: 1) fetal betamethasone injection 48 h before delivery stabilizes GFR and significantly alters endocrine function in preterm newborn lambs, and 2) the addition of T4 does not augment betamethasone-induced renal and endocrine responses.

Although the benefits of antenatal hormone treatment are well accepted, most studies have reported only pulmonary effects. There is evidence of beneficial cardiovascular and metabolic effects in studies using chronically catheterized animals; however because of the route of administration, the results are not directly applicable to clinical strategies. We previously demonstrated significant pulmonary effects in animals treated antenatally with a single, direct fetal, intramuscular injection of glucocorticoids. This study was performed to determine the effects of a single fetal injection of betamethasone (BETA) alone or in combination with thyroxine (T4) on cardiovascular and metabolic responses after preterm birth. Hemodynamic and metabolic responses at birth were determined in fetuses (126-d gestation; term = 150 d) treated with ultrasound-guided intramuscular injections of 0.5 mg/kg BETA (n = 7), BETA plus 60 g/kg T4 (n = 7), or saline (SAL, n = 9). After 48 h, lambs were delivered by cesarean section and studied for 3 h. BETA treatment increased mean arterial blood pressure [56 +/- 6 (SEM) versus 42 +/- 3 mm Hg], heart rate (152 +/- 5 versus 123 +/- 4 beats/min), and cardiac output (467 +/- 17 versus 349 +/- 36 mL/min/kg) versus SAL. Responses of BETA+T4-treated animals were not different from animals treated with BETA alone. Glucose and FFA were similar among all groups. The increase in catecholamine levels normally seen at birth was significantly attenuated in both the BETA and BETA+T4-treated animals. A single, intramuscular injection of glucocorticoids 48 h before delivery improves cardiovascular responses to preterm birth. This effect is not augmented by concomitant administration of T4.

Atrial natriuretic factor (ANF) has been identified in fetal and newborn mammals, and considerable data regarding fetal ANF metabolism are available. However, there is limited information concerning ANF receptors or receptor ontogenesis in developing mammals. We measured ANF receptor binding capacity, affinity, and ANF-induced cyclic GMP (cGMP) generation in isolated renal glomeruli from fetal (29 d gestation, term = 31 d), newborn (3 d), juvenile (28 d), and adult rabbits. The (mean +/- SEM) glomerular receptor binding capacity values for ANF in fetal and newborn animals (10 +/- 1 and 12 +/- 3 fmol/mg protein) were similar and significantly lower than the values for juvenile and adult animals (30 +/- 8 and 74 +/- 15 fmol/mg protein, respectively). In contrast, there were no significant differences in ANF receptor affinity values or dose-dependent increases in ANF-stimulated cGMP generation among the age groups studied. In competition studies, we observed effective displacement of 125I-ANF by C-ANF4-23, a ring-deleted ANF analogue, in adult, juvenile, and newborn glomeruli; however, C-ANF displaced only about 50% of the 125I-ANF in fetal tissue. The addition of C-ANF did not elicit cGMP generation, nor did C-ANF affect ANF-induced cGMP generation in fetal, newborn, or adult glomeruli. These results indicate that 1) the ANF receptor-guanylate cyclase system is intact in 29-d fetal rabbit glomeruli, and 2) the ANF-induced cGMP formation is similar in fetal and adult animals, whereas receptor binding capacity is relatively higher in adult glomeruli. These results suggest a higher proportion of nonguanylate cyclase-coupled ANF receptors in the mature rabbit.

The proposed actions of atrial natriuretic factor (ANF) are mediated through specific plasma membrane (R1) receptors coupled to guanylate cyclase. A second receptor, R2, has been characterized by its ability to bind to an acyclic, truncated ANF analog (C-ANF4-23). The ANF-R2 receptor has not been identified in the fetus. Our study was conducted to determine the effects of C-ANF on fetal renal and cardiovascular function and plasma ANF clearance rates. Chronically catheterized ovine fetuses (n = 6) at 111 to 117 d gestation (term 145 d) received a C-ANF infusion (1 microgram/min/kg) for 30 min followed by a combined infusion of C-ANF and ANF (C-ANF, 1 microgram/min/kg; ANF, 100 ng/min/kg) for an additional 30 min. C-ANF infusion significantly increased (mean +/- SEM) plasma ANF concentration (437 +/- 45 to 1067 +/- 297 pg/mL), urinary flow rate (0.26 +/- 0.04 to 0.38 +/- 0.07 mL/min/kg), sodium excretion (12.9 +/- 3.5 to 21.7 +/- 6.1 mumol/min/kg), and osmolar clearance (0.14 +/- 0.02 to 0.21 +/- 0.04 mL/min/kg) (p less than 0.05). The combined C-ANF/ANF infusion further increased plasma ANF concentration to 2394 +/- 532 pg/mL and resulted in significant increases in urinary flow rate, sodium excretion, osmolar clearance, GFR, and free water clearance compared with C-ANF infusion alone (p less than 0.05). These renal responses, however, were not significantly different from the responses to ANF infusion alone (100 ng/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the effect of prolactin (PRL) on transplacental water flow, we infused mannitol (500 ml; 20% solution) over 10 min into five chronically catheterized ewes (121-134 days' gestation), producing a peak maternal plasma osmolality by 10 min and fetal osmolality by 20 min. One day before or after, an identical amount of mannitol was infused into the same ewe during the 2nd h of a 2-h infusion of PRL (40 +/- 2.2 micrograms/h) into a fetal leg vein. Mean (+/- SE) fetal plasma PRL levels were 6.9 +/- 3.2 ng/ml at baseline. Steady state fetal PRL levels were 17.7 +/- 7.4 ng/ml during PRL infusion. Maternal mannitol infused without administration of PRL to the fetus evoked a rise in fetal plasma osmolality similar to that following maternal mannitol during PRL administration to the fetus. Thus, as shown previously, PRL affects water permeability across the membranous chorioamnion, whereas results of the present study indicate that the hormone does not affect water transfer across the ovine chorionic villi (placenta).

Atrial natriuretic factor (ANF) is a class of diuretic and natriuretic peptides secreted by mammalian cardiac atria. Although basal plasma ANF levels in the ovine fetus are elevated relative to the adult, fetal secretion of ANF increases in response to intravascular isotonic saline infusion. Recent in vitro and in vivo studies indicate that ANF secretion also may be stimulated by increased plasma osmolality and/or sodium concentration. The present studies were conducted to determine if volume expansion associated with increased plasma osmolality would further augment ANF secretion in the ovine fetus. In response to successive 30-min intravenous infusions of 3% saline at 0.5 and 1.0 ml/kg/min fetal plasma ANF significantly increased from a basal level of 98 +/- 31 pg/ml to a peak of 439 +/- 42 pg/ml (p less than 0.05). During a 30-min postinfusion recovery period, fetal plasma ANF significantly decreased from peak values to 224 +/- 10 pg/ml (p less than 0.05), although remaining above basal levels. Fetal plasma osmolality significantly increased from 300 +/- 2 mosmol to 325 +/- 3 mosmol (p less than 0.05) whereas fetal plasma arginine vasopressin increased from 1.9 +/- 0.4 to 10.9 +/- 7.0 pg/ml (p less than 0.05) at the conclusion of the 3% saline infusion. During the saline infusion a significant increase in fetal heart rate and decrease in fetal hematocrit were noted. Fetal blood pressure and maternal plasma ANF and arginine vasopressin concentrations remained unchanged. Despite the potential stimulatory effects of hyperosmolality, increased plasma arginine vasopressin, and intravascular volume expansion, the increase in fetal plasma ANF in the present study did not exceed that induced by isotonic saline alone.(ABSTRACT TRUNCATED AT 250 WORDS)