Antenatal betamethasone administration has a dual effect on adult sheep vascular reactivity.
The effect of antenatal steroids on blood pressure in humans remains an unresolved question. Here we report the effects of prenatal exposure to clinically relevant doses of betamethasone on endothelial and/or vascular smooth muscle function. Pregnant sheep were randomly treated with betamethasone (0.17 mg/kg) or vehicle at 80 and 81 d of gestation. We studied arterial segments (4th-5th generation) of the right brachial artery obtained at 1-2 y of age under general anesthesia. We demonstrate that in brachial arteries of steroid exposed offspring: KCl induced contraction is increased after endothelium removal or incubation with inhibitors of nitric oxide synthase or cyclooxygenase; acetylcholine-induced relaxation is increased; sensitivity to endothelin-1 (ET-1) is increased and this effect is decreased by the ETB antagonist BQ-788. These data suggest that, in sheep treated with clinically relevant doses of betamethasone at a gestational stage when human fetuses are routinely exposed to glucocorticoids, there is a dual effect of betamethasone on the adult sheep brachial artery, i.e. endothelial dysfunction with an impairment of endothelin-1 ETB receptor-induced release of nitric oxide and an increased contribution of the ETB receptor in smooth muscle to the contractile effects of ET-1.
Pulgar
Victor M
VM
Center for Research in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Figueroa
Jorge P
JP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007273:Injections, Intramuscular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D044023:Receptor, Endothelin B / Q000502:physiology; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D005938:Glucocorticoids; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D011189:Potassium Chloride; D001623:Betamethasone; D000109:Acetylcholine