Document Detail

Angiotensin-(1-7) deficiency and baroreflex impairment precede the antenatal Betamethasone exposure-induced elevation in blood pressure.
MedLine Citation:
PMID:  22215705     Owner:  NLM     Status:  MEDLINE    
Betamethasone is administered to accelerate lung development and improve survival of premature infants but may be associated with hypertension later in life. In a sheep model of fetal programming resulting from exposure at day 80 of gestation to Betamethasone (Beta-exposed), adult sheep at 6 to 9 months or 1.8 years of age have elevated mean arterial pressure (MAP) and attenuated spontaneous baroreflex sensitivity (sBRS) for control of heart rate compared to age-matched controls associated with imbalances in angiotensin (Ang) II vs Ang-(1-7) tone. At 6 weeks of age, evoked BRS is already low in the Beta-exposed animals. In this study, we assessed the potential contribution of the renin-angiotensin system to the impaired sBRS. Female lambs (6 weeks old) with Beta exposure in utero had similar MAP to control lambs (78±2 vs 77±2 mm Hg, n=4-5 per group), but lower sBRS (8±1 vs 16±3 ms/mm Hg; P<0.05) and impaired heart rate variability. Peripheral AT1 receptor blockade using candesartan lowered MAP in both groups (≈10 mm Hg) and improved sBRS and heart rate variability in Beta-exposed lambs to a level similar to control. AT7 receptor blockade by infusion of D-ala Ang-(1-7) (700 ng/kg/min for 45 minutes) reduced sBRS 46%±10% in Beta-exposed vs in control lambs (P<0.15) and increased MAP in both groups (≈6±2 mm Hg). Our data reveal that Beta exposure impairs sBRS and heart rate variability at a time point preceding the elevation in MAP via mechanisms involving an imbalance in the Ang II/Ang-(1-7) ratio consistent with a progressive loss in Ang-(1-7) function.
Hossam A Shaltout; James C Rose; Mark C Chappell; Debra I Diz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-03
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-04-20     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-8     Citation Subset:  IM    
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Hanes Building, 6th floor, Medical Center Boulevard, Winston-Salem, NC 27157-1032, USA.
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MeSH Terms
Angiotensin I / deficiency*,  drug effects,  pharmacology
Angiotensin II Type 1 Receptor Blockers / pharmacology
Animals, Newborn
Baroreflex / drug effects,  physiology*
Benzimidazoles / pharmacology
Betamethasone / adverse effects*,  pharmacology
Blood Pressure / drug effects,  physiology
Disease Models, Animal
Glucocorticoids / adverse effects,  pharmacology
Heart Rate / drug effects
Hypertension / chemically induced*,  physiopathology*
Peptide Fragments / deficiency*,  drug effects,  pharmacology
Prenatal Exposure Delayed Effects / chemically induced*,  physiopathology*
Receptor, Angiotensin, Type 1 / drug effects
Tetrazoles / pharmacology
Grant Support
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Glucocorticoids; 0/Peptide Fragments; 0/Receptor, Angiotensin, Type 1; 0/Tetrazoles; 0/angiotensin I (1-7); 378-44-9/Betamethasone; 9041-90-1/Angiotensin I; S8Q36MD2XX/candesartan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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