| Angiotensin-(1-7) deficiency and baroreflex impairment precede the antenatal Betamethasone exposure-induced elevation in blood pressure. | |
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MedLine Citation:
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PMID: 22215705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hossam A Shaltout; James C Rose; Mark C Chappell; Debra I Diz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-03 |
Journal Detail:
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Title: Hypertension Volume: 59 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-25 Completed Date: 2012-04-20 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 453-8 Citation Subset: IM |
Affiliation:
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Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Hanes Building, 6th floor, Medical Center Boulevard, Winston-Salem, NC 27157-1032, USA. hshaltou@wfubmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin I
/
deficiency*,
drug effects,
pharmacology Angiotensin II Type 1 Receptor Blockers / pharmacology Animals Animals, Newborn Baroreflex / drug effects, physiology* Benzimidazoles / pharmacology Betamethasone / adverse effects*, pharmacology Blood Pressure / drug effects, physiology Disease Models, Animal Female Glucocorticoids / adverse effects, pharmacology Heart Rate / drug effects Hypertension / chemically induced*, physiopathology* Peptide Fragments / deficiency*, drug effects, pharmacology Pregnancy Prenatal Exposure Delayed Effects / chemically induced*, physiopathology* Receptor, Angiotensin, Type 1 / drug effects Sheep Tetrazoles / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HD-17644/HD/NICHD NIH HHS; HD-47584/HD/NICHD NIH HHS; HL-51952/HL/NHLBI NIH HHS; HL-56973/HL/NHLBI NIH HHS; R01 HD017644/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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