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Late-gestation betamethasone enhances coronary artery responsiveness to angiotensin II in fetal sheep. Am J Physiol Regul Integr Comp Physiol 2004 Jan;286(1):R80-8

Date

09/27/2003

Pubmed ID

14512274

DOI

10.1152/ajpregu.00421.2003

Scopus ID

2-s2.0-0346096880 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

Antenatal glucocorticoids are used to promote the maturation of fetuses at risk for preterm delivery. While perinatal glucocorticoid exposure has clear immediate benefits to cardiorespiratory function, there is emerging evidence of adverse long-term effects. To determine if antenatal betamethasone alters vascular reactivity, we examined isometric contraction of endothelium-intact coronary and mesenteric arteries isolated from twin fetal sheep at 121-124 days gestation (term being 145 days). One twin received betamethasone (10 microg/h iv) while the second twin received vehicle (0.9% NaCl) for 48 h immediately before the final physiological measurements and tissue harvesting. Fetuses that received betamethasone had higher mean arterial blood pressures than the saline-treated twin controls (53 +/- 1 vs. 48 +/- 1 mmHg, P < 0.05). Coronary vessels from betamethasone-treated fetuses exhibited enhanced peak responses to ANG II (72 +/- 17 vs. 23 +/- 6% of the maximal response to 120 mM KCl, P < 0.05). There was no significant difference in response of the coronary arteries to other vasoactive compounds [KCl, U-46619, sodium nitroprusside, 8-bromo-cGMP (8-BrcGMP), isoproterenol, and forskolin]. Contractile responses to ANG II were similar in betamethasone and control mesenteric arteries (48 +/- 17 vs. 36 +/- 12% of the maximal response to 10-6 M U-46619). Western blot analysis revealed AT1 receptor protein expression was increased by betamethasone in coronary but not in mesenteric arteries. These findings demonstrate that antenatal betamethasone exposure enhances coronary but not mesenteric artery vasoconstriction to ANG II by selectively upregulating coronary artery AT1 receptor protein expression.

Author List

Roghair RD, Lamb FS, Bedell KA, Smith OM, Scholz TD, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Arteries
Betamethasone
Coronary Vessels
Drug Administration Schedule
Drug Synergism
Female
Fetus
Gestational Age
Glucocorticoids
Immunoblotting
Immunohistochemistry
Mesenteric Arteries
Pregnancy
Receptor, Angiotensin, Type 1
Sheep
Vasoconstriction
Vasoconstrictor Agents