title: Large conductance Ca2+-activated K+ channels modulate uterine α1-adrenergic sensitivity in ovine pregnancy.
abstract: The uteroplacental vasculature is refractory to α-adrenergic stimulation, and large conductance Ca(2+)-activated K(+) channels (BK(Ca)) may contribute. We examined the effects of uterine artery (UA) BK(Ca) inhibition with tetraethylammonium (TEA) on hemodynamic responses to phenylephrine (PE) at 101 to 117 days and 135 to 147 days of ovine gestation, obtaining dose responses for mean arterial pressure (MAP), heart rate (HR), and uteroplacental blood flow (UPBF) and vascular resistance (UPVR) before and during UA TEA infusions. The UA α(1)-adrenergic receptors (α1-ARs) were assessed. The PE increased MAP and UPVR and decreased HR and UPBF dose dependently at both gestations (P < .001, analysis of variance). The %▵MAP was less at 135 to 147 days before and during TEA infusions (P ≤ .008); however, responses during TEA were greater (P ≤ .002). The PE increased %▵UPVR>>%▵MAP, thus %▵UPBF fell. The TEA enhanced PE-mediated increases in %▵UPVR at 135 to 147 days (P ≤ .03). The UA α(1)-AR expression was unchanged in pregnancy. Uterine vascular responses to PE exceed systemic vascular responses throughout pregnancy and are attenuated by BK(Ca) activation, suggesting BK(Ca) protect UPBF.
authors.affiliation: 1Department of Pediatrics, Division of Neonatal-Perinatal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rosenfeld
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.forename: Xiao-tie
authors.initials: XT
authors.lastname: Liu
authors.forename: Timothy
authors.initials: T
authors.lastname: Roy
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007261:Infusions, Intra-Arterial; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D021041:Placental Circulation / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D012756:Sheep; D013997:Time Factors; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine
keywords: pressor responses; uteroplacental blood flow; vascular sensitivity; α1-adrenergic receptors
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