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1 Department of Pediatrics, University of Iowa, Iowa City, IA, USA
2 Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
* To whom correspondence should be addressed. E-mail: jeffrey-segar{at}uiowa.edu.
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/day) 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 months 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 angiotensin II, relative to controls. In 4 month-old lambs, prenatal dexamethasone exposure significantly increased coronary artery vasoconstriction to angiotensin II, acetylcholine and U46619, but not KCl. In contrast, postnatal mesenteric artery reactivity was unaltered by steroid exposure. Compared to fetal mesenteric reactivity, postnatal mesenteric reactivity to angiotensin II, phenylephrine, and U46619 was diminished, while the response to 120 mmol/L KCl was heightened. Coronary artery angiotensin 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.
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