Abstract 1313 Poster Session I, Saturday, 5/1 (poster 51)

Antenatal glucocorticoid (GC) administration improves cardiovascular function after premature birth, as demonstrated by increased postnatal heart rate and blood pressure. The mechanisms by which antenatal GC facilitate postnatal circulatory function are uncertain, but may be related to augmented angiotensinergic functions, including increased vascular reactivity to angiotensin II (AII). In addition, we have shown that GC administration evokes a more pronounced sympathetic response at birth in prematurely delivered lambs and attenuates baroreflex mediated changes in heart rate (HR) (Am J Physiol 274:R160,1998), changes consistent with known effects of AII (via AT1 receptor) on autonomic function. Therefore, to test the hypothesis that the effects of GC on postnatal cardiovascular and sympathetic activity are mediated via the renin-angiotensin system, we studied the effects of AT1 receptor blockade on postnatal changes in HR, mean arterial blood pressure (MABP), renal sympathetic nerve activity (RSNA) and baroreflex control of HR in GC treated preterm lambs. After maternal administration of betamethasone (12 mg IM 48 and 24 h before delivery), chronically instrumented preterm lambs (118-123 d gestation, term 145 d) were studied before and after delivery by cesarean section; lambs received either the AT1 receptor antagonist losartan (10 mg iv, n = 6), or saline (n = 6) 1 h prior to delivery. Compared with fetal values, GC alone animals demonstrated significant increases (p<0.05) in MABP (47±2 to 58±2 mmHg) and RSNA (181±80% of fetal value) one hour after delivery, consistent with our previous results. Losartan had no effect on fetal resting HR, MABP or RSNA. Following delivery, losartan treated lambs displayed increases in MABP (48±1 to 55±3 mmHg) and RSNA (198±96% of fetal value) similar to values seen in GC alone lambs. No significant differences in HR were detected between animals before or after birth. The sensitivity of baroreflex mediated changes in HR in response to increases in MABP were also similar in both groups of animals before and after birth. Plasma AII levels increased two-fold after birth in losartan animals (p<0.05) whereas no change occurred in GC alone lambs. These results confirm our previous findings that antenatal GC augment sympathetic responses at birth in premature lambs. However, the data demonstrate that the observed postnatal increases in MABP and RSNA are not mediated by stimulation of peripheral AT1 receptors. We speculate that augmented cardiovascular function in GC treated premature lambs is dependent in part upon a generalized sympathoexcitatory response and that this effect of GC is mediated by central mechanisms.