Impact of maternal dexamethasone on coronary PGE(2) production and prostaglandin-dependent coronary reactivity.

Roghair RD, Volk KA, Lamb FS, Segar JL
Am J Physiol Regul Integr Comp Physiol. 2012 303 (5): R513-9

PMID: 22832534 · PMCID: PMC3468415 · DOI:10.1152/ajpregu.00658.2011

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 E(2) (PGE(2)) helps maintain coronary dilation, but PGE(2) production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE(2) 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 PGE(2) 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 PGE(2) 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.

MeSH Terms (19)

Angiotensin II Animals Cells, Cultured Coronary Vessels Cyclooxygenase Inhibitors Dexamethasone Dinoprostone Female Glucocorticoids Indomethacin Models, Animal Muscle, Smooth, Vascular Pregnancy Prenatal Exposure Delayed Effects Prostaglandins Sheep Vasoconstriction Vasoconstrictor Agents Vasodilation

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