Late-gestation betamethasone enhances coronary artery responsiveness to angiotensin II in fetal sheep.
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.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000196:embryology; D001623:Betamethasone / Q000008:administration & dosage*; D003331:Coronary Vessels / Q000196:embryology*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008638:Mesenteric Arteries / Q000196:embryology; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012756:Sheep; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D005938:Glucocorticoids; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001623:Betamethasone