Maternal dexamethasone treatment alters myosin isoform expression and contractile dynamics in fetal arteries.
We tested the hypothesis that maternal glucocorticoid treatment modulates 17-kDa myosin light chain (myosin LC17) isoform expression and contractile dynamics in fetal ovine carotid arteries. In the single course group, ewes received 6 mg dexamethasone or placebo over 48 h. In the repeated course group, ewes received 6 mg dexamethasone or placebo weekly for 5 wk. In response to 1 microM phenylephrine, arteries from fetuses of dexamethasone-treated ewes exhibited biphasic contractions, characterized by an intermediate relaxation phase. The relaxation rate constant was significantly higher in arteries from the fetuses of dexamethasone than placebo-treated ewes. The observed biphasic contractions suggest the appearance of functional sarcoplasmic reticulum in the arteries from the fetuses of dexamethasone-treated ewes. The myosin LC17(a) isoform expression was lower in the arteries from the fetuses of the placebo-treated ewes than in those from the ewes. Repeated maternal administration of dexamethasone induced an almost twofold increase in myosin LC17(a) isoform expression in the fetal arteries. In contrast, maternal myosin LC17a isoform expression was not affected by dexamethasone treatment. We speculate that dexamethasone-induced increases in fetal myosin LC17(a) isoform expression represent accelerated differentiation of a subpopulation of vascular smooth muscle cells from the fetal to adult phenotype.
Hai
Chi-Ming
CM
Department of Molecular Pharmacology, Physiology and Biotechnology, School of Medicine, Brown University, Box G-B3, Providence, RI 02912, USA. chi-ming_hai@brown.edu
Sadowska
Grazyna
G
Francois
Louise
L
Stonestreet
Barbara S
BS
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000098:blood supply; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000209:etiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D010919:Placebos; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids; D018994:Myosin Light Chains; D010919:Placebos; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D003907:Dexamethasone