Antenatal betamethasone alters vascular reactivity in adult female ovine cerebral arteries.
Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep, whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there seemed to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.
Eckman
Delrae M
DM
Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. deckman@wfubmc.edu
Kerr
Brady A
BA
Fuloria
Mamta
M
Simandle
Steve A
SA
Watt
Suzanne E
SE
Rose
James C
JC
Figueroa
Jorge P
JP
D000367:Age Factors; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage* / Q000633:toxicity; D001794:Blood Pressure; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000633:toxicity; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D014665:Vasodilator Agents; D001623:Betamethasone; D019001:Nitric Oxide Synthase