Faculty Collaboration Database

Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II. Am J Physiol Regul Integr Comp Physiol 2001 Mar;280(3):R646-54

Date

02/15/2001

Pubmed ID

11171641

DOI

10.1152/ajpregu.2001.280.3.R646

Scopus ID

2-s2.0-0034992429 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

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.

Author List

Segar JL, Bedell KA, Smith OJ

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin Receptor Antagonists
Animals
Animals, Newborn
Autonomic Nervous System
Betamethasone
Blood Pressure
Cardiovascular Physiological Phenomena
Cardiovascular System
Female
Gestational Age
Glucocorticoids
Heart Rate
Kidney
Losartan
Pregnancy
Pressoreceptors
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Renin-Angiotensin System
Sheep
Sympathetic Nervous System