Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II

The mechanisms by which antenatal glucocorticoids facilitate postnatal circ ulatory function in preterm infants are uncertain but may be related to aug mented angiotensinergic functions. To test the hypothesis that the effects of glucocorticoids on postnatal cardiovascular and sympathetic activity are mediated via the renin-angiotensin system, we studied the effects of AT(1) receptor blockade on postnatal changes in heart rate (HR), mean arterial b lood pressure (MABP), renal sympathetic nerve activity (RSNA), and barorefl ex control of HR in prematurely delivered lambs. After maternal administrat ion of betamethasone (12 mg im 48 and 24 h before delivery), chronically in strumented preterm lambs (118- to 123-day gestation, term 145 days) were st udied before and after delivery by cesarean section; fetuses received eithe r the AT1 receptor antagonist losartan (10 mg iv, n = 6) or saline (n = 6) 1 h before delivery. A third group of animals (n = 6) received losartan wit hout prior exposure to betamethasone. Compared with fetal values, betametha sone-treated animals demonstrated significant increases (P < 0.05) in MABP (47 +/- 2 to 58 +/- 2 mmHg) and RSNA (181 +/- 80% of fetal value) 1 h after delivery. Betamethasone + losartan-treated lambs also displayed increases in MABP (48 +/- 1 to 55 +/- 3 mmHg) and RSNA (198 +/- 96% of fetal value) 6 0 min after birth, similar to betamethasone alone lambs. Losartan alone tre ated animals had no postnatal increase in either MABP or RSNA, responses si milar to those seen in nontreated sheep delivered at the same gestational a ge. The sensitivity of baroreflex-mediated changes in HR in response to inc reases in MABP was less in both groups of betamethasone-treated animals; no effect was seen with losartan. These results suggest the postnatal increas es in MABP and RSNA seen with antenatal glucocorticoid treatment are not me diated by stimulation of peripherally accessible AT(1) receptors. We specul ate that augmented cardiovascular function in glucocorticoid-treated premat ure lambs is dependent, in part, on a generalized sympathoexcitatory respon se and that this effect of glucocorticoids is mediated by central mechanism s.