Journal article
Impact of maternal dexamethasone on coronary PGE2 production and prostaglandin-dependent coronary reactivity
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.303(5), pp.R513-R519
09/01/2012
DOI: 10.1152/ajpregu.00658.2011
PMCID: PMC3468415
PMID: 22832534
Abstract
Intrauterine growth restriction is associated with increased fetal glucocorticoid exposure and an increased risk of adult coronary artery disease. Coronary arteries from sheep exposed to early gestation dexamethasone (Dex) have increased constriction to angiotensin II (ANG II). Prostaglandin E2 (PGE2) helps maintain coronary dilation, but PGE2 production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE2 production with subsequent increases in coronary reactivity. Dex was administered to ewes at 27–28 days gestation (term 145 days). Coronary reactivity was assessed by wire myography in offspring at 4 mo of age ( N = 5 to 7). Coronary smooth muscle cells were cultured and prostaglandin production was measured after 90 min incubation with radiolabeled arachidonate. Coronary myocytes from Dex-exposed lambs had a significant decrease in PGE2 production that was reversed with ANG II incubation. Dex-exposed coronary arteries had increased constriction to ANG II and attenuated dilatation to arachidonic acid, with the greatest difference seen after the endothelium was inactivated by rubbing. Preincubation with the cyclooxygenase (COX) inhibitor indomethacin altered control responses and recapitulated the heightened coronary tone seen following Dex exposure. We conclude that impaired coronary smooth muscle COX-mediated PGE2 production contributes to the coronary dysfunction elicited by early gestation Dex. Programmed inhibition of vasodilatory prostanoid production may link an adverse intrauterine environment with adult coronary artery disease.
Details
- Title: Subtitle
- Impact of maternal dexamethasone on coronary PGE2 production and prostaglandin-dependent coronary reactivity
- Creators
- Robert D Roghair - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IowaKenneth A Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IowaFred S Lamb - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IowaJeffrey L Segar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.303(5), pp.R513-R519
- DOI
- 10.1152/ajpregu.00658.2011
- PMID
- 22832534
- PMCID
- PMC3468415
- NLM abbreviation
- Am J Physiol Regul Integr Comp Physiol
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Language
- English
- Date published
- 09/01/2012
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093342802771
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