In fetal sheep, angiotensin-converting enzyme (ACE) concentration in the lungs and kidneys increases near term in parallel with the prepartum cortisol surge (Forhead et al. 2000). Indeed, an exogenous infusion of cortisol in immature fetuses elevates pulmonary, but not renal, ACE to levels seen close to term (Forhead et al. 2000). In clinical practice, synthetic glucocorticoids such as dexamethasone (DEX) are administered to pregnant women at risk of preterm delivery in order to accelerate fetal maturation. However, the effects of DEX on tissue ACE in utero are unknown. Therefore, this study examined pulmonary and renal ACE concentrations in sheep fetuses infused with DEX, using a dose that increases plasma DEX to around one-fifth of the concentration measured in human infants delivered after maternal DEX treatment (Fletcher et al. 2000).

All procedures were carried out according to UK legislation. Under general anaesthesia (20 mg kg^-1 sodium pentobarbitone I.V.), lungs and kidneys were collected from 16 sheep fetuses delivered by Caesarean section at 125-129 days of gestation. The fetuses were humanely killed by an overdose of sodium pentobarbitone. Ten of the fetuses were infused intravenously with either DEX (45-60 µg kg^-1 day^-1, n = 6) or saline (0.9 % NaCl, 2.5 ml day^-1, n = 4) for the previous 2 days; the remaining six control fetuses were not catheterised. Intravascular catheters were implanted under general anaesthesia (1.5 % halothane in O₂-N₂O) at least 5 days before the infusion began. In the catheterised fetuses, mean arterial blood pressure (BP) was measured on each day of infusion. Tissue ACE concentration (as a proxy measure of activity) and protein content were determined using spectrophotometric and Lowry methods, respectively. Data (means ± S.E.M.) were analysed by unpaired t test and linear regression.

Pulmonary ACE concentration was significantly greater in the DEX-infused fetuses than in the control fetuses (P < 0.005, Fig. 1). Renal ACE was not affected by DEX infusion (Fig. 1). On the last day of infusion, the change in BP from pre-infusion values was significantly greater in the DEX-infused fetuses (6.8 ± 1.5 mmHg, n = 6) compared with the control fetuses (1.6 ± 0.6 mmHg, n = 4, P < 0.05). Overall, significant positive correlations were observed between pulmonary ACE concentration and both BP on the last day of infusion (r = 0.70, P < 0.05, n = 10) and the increment in BP during the infusion (r = 0.67, P < 0.05, n = 10).

Therefore, in the sheep, fetal treatment with DEX increases pulmonary but not renal ACE concentration. The rise in pulmonary ACE seen in the DEX-infused fetuses may contribute, in part, to the glucocorticoid-induced hypertension. These findings may have important implications for cardiovascular and renal development in fetuses exposed to antenatal glucocorticoid treatment.

This work was supported by Tommy’s Campaign.

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Figure 1. Mean (± S.E.M.) pulmonary and renal ACE concentrations in control (n = 10) and DEX-infused (n = 6) fetuses. * Significantly different from control fetuses, P < 0.005.