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Deleterious Cardiovascular Effects of Antenatal Betamethasone Exposure in Young and Adult Sheep
Author(s) -
Shaltout Hossam Abdelnaby,
Figueroa Jorge P,
Rose James C,
Chappell Mark C,
Averill David B,
Diz Debra I
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1129.16
Subject(s) - betamethasone , medicine , ventricle , heart rate , candesartan , blood pressure , baroreflex , endocrinology , mean arterial pressure , cardiology , gestational age , angiotensin ii , pregnancy , biology , genetics
Betamethasone (Beta) administration prior to premature delivery in early third trimester is employed to accelerate lung development and improve survival. Male adult sheep (1.8 years) exposed at 80th day of gestation to Beta (Ad‐Beta) had elevated arterial pressure (MAP), increased left ventricle to body weight ratio (LV/BW), and attenuated baroreflex sensitivity for control of heart rate (BRS) compared to age‐matched controls (Ad‐Veh). We have now determined that young sheep (0.5 years) exposed antenatally to Beta (Y‐Beta) had higher MAP (95 ± 2 vs 77 ± 2 mm Hg; p < 0.05) and lower BRS (3.9 ± 1.2 vs 10.4 ± 1.8 ms/mm Hg; p < 0.05) compared with Y‐Veh. However, at this age there was no difference in LV/BW between Y‐Beta and Y‐Veh groups. The AT1 angiotensin antagonist candesartan (0.3 mg/kg, iv) normalized MAP and improved BRS in Y‐Beta sheep. Heart rate variability (HRV) and blood pressure variability (BPV), measured by time and frequency domain analysis, revealed that Y‐Beta sheep had significantly lower HRV (SDRR, rMSSD, LFRRI, and HFRRI) compared with Y‐Veh and higher BPV (SDMAP, LFSAP). Candesartan partially restored HRV in Y‐Beta sheep and fully corrected BPV. Thus, in utero exposure to Beta increases MAP and impairs baroreflex control of heart rate in young sheep. The deleterious actions of antenatal steroids persisted into adulthood, likely contributing to LV hypertrophy in adult sheep. HD047584