Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II.
The mechanisms by which antenatal glucocorticoids facilitate postnatal circulatory function in preterm infants are uncertain but may be related to augmented 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 blood pressure (MABP), renal sympathetic nerve activity (RSNA), and baroreflex control of HR in prematurely delivered lambs. After maternal administration of betamethasone (12 mg im 48 and 24 h before delivery), chronically instrumented preterm lambs (118- to 123-day gestation, term 145 days) were studied before and after delivery by cesarean section; fetuses received either the AT(1) 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 without prior exposure to betamethasone. Compared with fetal values, betamethasone-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) 60 min after birth, similar to betamethasone alone lambs. Losartan alone treated animals had no postnatal increase in either MABP or RSNA, responses similar to those seen in nontreated sheep delivered at the same gestational age. The sensitivity of baroreflex-mediated changes in HR in response to increases in MABP was less in both groups of betamethasone-treated animals; no effect was seen with losartan. These results suggest the postnatal increases in MABP and RSNA seen with antenatal glucocorticoid treatment are not mediated by stimulation of peripherally accessible AT(1) receptors. We speculate that augmented cardiovascular function in glucocorticoid-treated premature lambs is dependent, in part, on a generalized sympathoexcitatory response and that this effect of glucocorticoids is mediated by central mechanisms.
Segar
J L
JL
Department of Pediatrics and the Cardiovascular Center, University of Iowa, Iowa City, Iowa 52242, USA. jeffrey-segar@uiowa.edu
Bedell
K A
KA
Smith
O J
OJ
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001623:Betamethasone / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D011247:Pregnancy; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012084:Renin-Angiotensin System / Q000502:physiology; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D005938:Glucocorticoids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D001623:Betamethasone; D019808:Losartan