title: Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.
abstract: Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;
authors.forename: Michelle
authors.initials: M
authors.lastname: Dreiling
authors.affiliation: b Institute of Lab Animal Sciences and Welfare, Jena University Hospital , Jena , Germany ;
authors.forename: Sabine
authors.initials: S
authors.lastname: Bischoff
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;
authors.forename: Rene
authors.initials: R
authors.lastname: Schiffner
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;
authors.forename: Sven
authors.initials: S
authors.lastname: Rupprecht
authors.affiliation: c Institute of Clinical Chemistry and Laboratory Medicine, Jena University Hospital , Jena , Germany ;
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.affiliation: b Institute of Lab Animal Sciences and Welfare, Jena University Hospital , Jena , Germany ;
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;|d Center for Sepsis Control and Care, Jena University Hospital , Jena , Germany ;
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.affiliation: e Department of Animal Science , University of Wyoming , Laramie , WY , USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: a Hans Berger Department of Neurology , Jena University Hospital , Jena , Germany ;
authors.forename: Florian
authors.initials: F
authors.lastname: Rakers
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D005333:Fetus / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology*; D012756:Sheep; D013312:Stress, Physiological / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D006854:Hydrocortisone
keywords: Placenta; adrenergic receptors; isolation stress; prenatal programming; sheep; stress transfer; urapidil