| Acute AT(1)-receptor blockade reverses the hemodynamic and baroreflex impairment in adult sheep exposed to antenatal betamethasone. | |
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MedLine Citation:
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PMID: 20543085 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To accelerate lung development and protect neonates from other early developmental problems, synthetic steroids are administered maternally in the third trimester, exposing fetuses that are candidates for premature delivery to them. However, steroid exposure at this point of gestation may lead to elevated blood pressure [mean arterial pressure (MAP)] during adolescence. We hypothesize that fetal exposure to steroids activates the renin-angiotensin system, inducing an elevation in blood pressure and attenuation of baroreflex sensitivity (BRS) that is angiotensin II dependent in early adulthood. To test this hypothesis, fetal sheep were exposed to betamethasone (Beta) or vehicle (control) administered to ewes at day 80 of gestation and delivered at full term. At 1.8 yr of age, male offspring were instrumented for conscious recording of MAP, heart rate, and measurement of BRS [as low-frequency-alpha, high-frequency-alpha, sequence (seq) UP, seq DOWN, and seq TOTAL]. Beta-exposed sheep (n = 6) had higher MAP than control sheep (n = 5) (93 + or - 2 vs. 84 + or - 2 mmHg, P < 0.01). Acute blockade of angiotensin type 1 receptors with candesartan (0.3 mg/kg iv) normalized MAP in Beta-exposed sheep (85 + or - 4 mmHg), with no effect in control sheep (82 + or - 3 mmHg). Before angiotensin type 1 blockade, BRS maximum gain was significantly lower in Beta-exposed vs. control sheep (11 + or - 3 vs. 26 + or - 3 ms/mmHg, P < 0.0.01). However, 45 min after candesartan injection, BRS was increased in Beta-exposed (21 + or - 5 ms/mmHg) and control (35 + or - 4 ms/mmHg) sheep. Heart rate variability (HRV) and blood pressure variability (BPV) revealed lower HRV (SD of beat-to-beat interval and root mean square of successive beat-to-beat differences in R-R interval duration) and higher BPV (SD of MAP, systolic arterial pressure in low-frequency range) in Beta-exposed sheep. Candesartan partially restored HRV in Beta-exposed sheep and fully corrected BPV. Thus, in utero exposure to synthetic glucocorticoids causes long-lasting programming of the cardiovascular system via renin-angiotensin system-dependent mechanisms. |
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Authors:
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Hossam A Shaltout; James C Rose; Jorge P Figueroa; Mark C Chappell; Debra I Diz; David B Averill |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-11 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H541-7 Citation Subset: IM |
Affiliation:
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Hypertension and Vascular Research Center, Wake Forest Univ. School of Medicine, Hanes Bldg., 6th floor, Medical Center Blvd., Winston-Salem, NC 27157-1032, USA. hshaltou@wfubmc.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Angiotensin II Type 1 Receptor Blockers / pharmacology* Animals Antihypertensive Agents / pharmacology* Baroreflex / drug effects* Benzimidazoles / pharmacology* Betamethasone / toxicity* Blood Pressure / drug effects Female Gestational Age Glucocorticoids / toxicity* Heart Rate / drug effects Hemodynamics / drug effects* Hypertension / chemically induced, physiopathology, prevention & control Male Pregnancy Prenatal Exposure Delayed Effects* Renin-Angiotensin System / 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 HD017644-25/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Glucocorticoids; 0/Tetrazoles; 139481-59-7/candesartan; 378-44-9/Betamethasone |
| Comments/Corrections | |
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