Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity

Robert D Roghair; Fred S Lamb; Francis J Miller Jr; Thomas D Scholz; Jeffrey L Segar

doi:10.1152/ajpregu.00165.2004

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Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity

Journal article

Peer reviewed

Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity

Robert D Roghair, Fred S Lamb, Francis J Miller Jr, Thomas D Scholz and Jeffrey L Segar

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.288(1), pp.R46-53

01/2005

DOI: 10.1152/ajpregu.00165.2004

PMID: 15217789

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Abstract

Excessive exposure of the fetus to maternally derived corticosteroids has been linked to the development of adult-onset diseases. To determine if early gestation corticosteroid exposure alters subsequent coronary artery reactivity, we administered dexamethasone (0.28 mg.kg(-1).day(-1)) to pregnant ewes at 27-28 days gestation (term being 145 days). Vascular responsiveness was assessed in endothelium-intact coronary and mesenteric arteries isolated from steroid-exposed and age-matched control fetal sheep at 123-126 days gestation and lambs at 4 mo of age. Lambs exposed to maternal dexamethasone had higher mean arterial blood pressures than the age-matched controls (93 +/- 3 vs. 83 +/- 5 mmHg, P < 0.05). Mesenteric arteries from the steroid-exposed fetuses displayed diminished responses to ANG II, relative to controls. In 4-mo-old lambs, prenatal dexamethasone exposure significantly increased coronary artery vasoconstriction to ANG II, ACh, and U-46619, but not KCl. In contrast, postnatal mesenteric artery reactivity was unaltered by steroid exposure. Compared with fetal mesenteric reactivity, postnatal mesenteric reactivity to ANG II, phenylephrine, and U-46619 was diminished, whereas the response to 120 mmol/l KCl was heightened. Coronary artery ANG II receptor protein expression was not significantly altered by steroid exposure in either age group. These findings demonstrate that early-gestation glucocorticoid exposure programs postnatal elevations in blood pressure and selectively enhances coronary artery responsiveness to second messenger-dependent vasoconstrictors. Glucocorticoid-induced alterations in coronary vascular smooth muscle structure or function may provide a mechanistic link between an adverse intrauterine environment and later cardiovascular disease.

Pregnancy

Carotid Arteries - drug effects

Angiotensin II - pharmacology

Coronary Vessels - drug effects

Mesenteric Arteries - physiology

Prenatal Exposure Delayed Effects

Coronary Vessels - physiology

Coronary Vessels - embryology

Mesenteric Arteries - drug effects

Fetus - physiology

Gestational Age

Vasoconstriction - drug effects

Fetus - drug effects

Animals

Dexamethasone - pharmacology

Carotid Arteries - embryology

Carotid Arteries - physiology

Glucocorticoids - pharmacology

Vascular Resistance - drug effects

Female

Sheep

Details

Title: Subtitle: Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity
Creators: Robert D Roghair - Department of Pediatrics, University of Iowa, Iowa City, USA
Fred S Lamb
Francis J Miller Jr
Thomas D Scholz
Jeffrey L Segar
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.288(1), pp.R46-53
DOI: 10.1152/ajpregu.00165.2004
PMID: 15217789
ISSN: 0363-6119
eISSN: 1522-1490
Grant note: K08 HL003669-05 / NHLBI NIH HHS R21 ES-012268 / NIEHS NIH HHS K08 HL003669-03 / NHLBI NIH HHS K08 HL003669-04 / NHLBI NIH HHS
Language: English
Date published: 01/2005
Academic Unit: Cardiology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Neonatology
Record Identifier: 9984093343402771

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33 Times Cited - Web of Science